CBL

Summary

Gene Symbol: CBL
Description: Cbl proto-oncogene
Alias: C-CBL, CBL2, FRA11B, NSLL, RNF55, E3 ubiquitin-protein ligase CBL, Cas-Br-M (murine) ecotropic retroviral transforming sequence, Cbl proto-oncogene, E3 ubiquitin protein ligase, RING finger protein 55, RING-type E3 ubiquitin transferase CBL, casitas B-lineage lymphoma proto-oncogene, fragile site, folic acid type, rare, fra(11)(q23.3), oncogene CBL2, proto-oncogene c-Cbl, signal transduction protein CBL
Species: human

Top Publications

  1. ncbi Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells
    L E Marengere
    Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada
    J Immunol 159:70-6. 1997
  2. pmc Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity
    D P Bonita
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 17:4597-610. 1997
  3. ncbi LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation
    W Zhang
    Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 5430, USA
    Cell 92:83-92. 1998
  4. ncbi The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase
    C A Joazeiro
    The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA
    Science 286:309-12. 1999
  5. ncbi Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1
    G Levkowitz
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Mol Cell 4:1029-40. 1999
  6. ncbi Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases
    N Zheng
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 102:533-9. 2000
  7. pmc Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation
    Kyohei Umebayashi
    Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Mol Biol Cell 19:3454-62. 2008
  8. ncbi Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G
    K A Reedquist
    Lymphocyte Biology Section, Division of Rheumatology and Immunology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:8435-42. 1996
  9. pmc SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling
    J Tang
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Department of Pediatrics, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:9775-80. 1999
  10. pmc Cbl controls EGFR fate by regulating early endosome fusion
    Gina D Visser Smit
    Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
    Sci Signal 2:ra86. 2009

Research Grants

  1. Novel TIRF microscopy analyzing trafficking & signaling at the cell cortex
    Derek Toomre; Fiscal Year: 2009
  2. Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte Death
    Abdelkarim Sabri; Fiscal Year: 2012
  3. Mitchell Kronenberg; Fiscal Year: 2014
  4. Scavenging of Reactive Oxygen and Nitrogen Species by Cobalamins
    NICOLA ELIZABETH BRASCH; Fiscal Year: 2011
  5. The Transcobalamin Receptor in Cobalamin Homeostasis
    Edward V Quadros; Fiscal Year: 2011
  6. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
  7. Jordan A Kreidberg; Fiscal Year: 2014
  8. GDNF and Ret are critical for glomerular development, maintenance, and protection
    CYNTHIA TSUI; Fiscal Year: 2013
  9. JENNIFER LYNN STRIPAY; Fiscal Year: 2015
  10. SPRY2 predicts survival post-chemotherapy in advanced ovarian cancer.
    Raymond P Perez; Fiscal Year: 2010

Detail Information

Publications268 found, 100 shown here

  1. ncbi Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells
    L E Marengere
    Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada
    J Immunol 159:70-6. 1997
    The molecular adapter c-Cbl is rapidly tyrosine phosphorylated following stimulation through the TCR and associates with Src homology domain-2 (SH2)/SH3 domain-containing adapters such as Grb2, Crk, and Crk-L, which interact with guanine ..
  2. pmc Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity
    D P Bonita
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 17:4597-610. 1997
    Recent studies have demonstrated that Cbl, the 120-kDa protein product of the c-cbl proto-oncogene, serves as a substrate of a number of receptor-coupled tyrosine kinases and forms complexes with SH3 and SH2 domain-containing proteins, ..
  3. ncbi LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation
    W Zhang
    Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 5430, USA
    Cell 92:83-92. 1998
    ..Its function is demonstrated by inhibition of T cell activation following overexpression of a mutant form lacking critical tyrosine residues. Therefore, we propose to name the molecule LAT-linker for activation of T cells...
  4. ncbi The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase
    C A Joazeiro
    The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA
    Science 286:309-12. 1999
    ..c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC ..
  5. ncbi Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1
    G Levkowitz
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Mol Cell 4:1029-40. 1999
    ..An in vitro reconstituted system indicates that Cbl adaptor proteins directly control downregulation of the receptor for the epidermal growth factor (EGFR) by ..
  6. ncbi Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases
    N Zheng
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 102:533-9. 2000
    Ubiquitin-protein ligases (E3s) regulate diverse cellular processes by mediating protein ubiquitination. The c-Cbl proto-oncogene is a RING family E3 that recognizes activated receptor tyrosine kinases, promotes their ubiquitination by a ..
  7. pmc Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation
    Kyohei Umebayashi
    Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Mol Biol Cell 19:3454-62. 2008
    c-Cbl is the E3 ubiquitin ligase that ubiquitinates the epidermal growth factor (EGF) receptor (EGFR)...
  8. ncbi Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G
    K A Reedquist
    Lymphocyte Biology Section, Division of Rheumatology and Immunology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:8435-42. 1996
    We and others have recently identified Cbl, the protein product of the c-cbl protooncogene, as an early tyrosine kinase substrate upon T cell activation and have shown that Cbl forms in vivo complexes with Src family tyrosine kinases, ..
  9. pmc SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling
    J Tang
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Department of Pediatrics, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:9775-80. 1999
    ..such as SLP-76, Vav, and LAT, positively regulate TCR-mediated signal transduction, whereas others, such as Cbl, play an inhibitory role...
  10. pmc Cbl controls EGFR fate by regulating early endosome fusion
    Gina D Visser Smit
    Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
    Sci Signal 2:ra86. 2009
    Amino acid residues 1 to 434 of the E3 ubiquitin ligase Cbl control signaling of the epidermal growth factor receptor (EGFR) by enhancing its ubiquitination, down-regulation, and lysosomal degradation...
  11. pmc Computational analysis of HIV-1 resistance based on gene expression profiles and the virus-host interaction network
    Tao Huang
    Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People s Republic of China
    PLoS ONE 6:e17291. 2011
    ..These proteins may be useful targets for AIDS prevention or therapy, as intervention in these pathways could disrupt communication with virus-targeted proteins and HIV-1 infection...
  12. ncbi Serine mutations that abrogate ligand-induced ubiquitination and internalization of the EGF receptor do not affect c-Cbl association with the receptor
    Morten P Oksvold
    Department of Pathology, University of Western Australia, Queen Elizabeth II Medical Center, Nedlands, Western Australia 6009, Australia
    Oncogene 22:8509-18. 2003
    ..We therefore tested the hypothesis that these mutations affect ligand-induced c-Cbl association with the receptor, leading to inhibited receptor ubiquitination...
  13. ncbi c-Cbl-mediated ubiquitinylation is required for epidermal growth factor receptor exit from the early endosomes
    Tommer Ravid
    Signal Transduction, Department of Internal Medicine, University of California, School of Medicine, Davis, CA 95616, USA
    J Biol Chem 279:37153-62. 2004
    ..In the present study we examined the role of the E3 ligase c-Cbl, as a possible link between oxidative stress, EGFR signaling, and tumorigenic responses...
  14. pmc A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation
    Steven Pennock
    Department of Cell Biology and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
    Mol Cell Biol 28:3020-37. 2008
    The precise role of Cbl in epidermal growth factor (EGF) receptor (EGFR) endocytosis and trafficking remains to be fully uncovered...
  15. pmc A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling
    Hadassa Waterman
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO J 21:303-13. 2002
    Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) is controlled by c-Cbl, a ubiquitin ligase that binds multiple signaling proteins, including the Grb2 adaptor...
  16. ncbi Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3zeta disrupt its interaction with Raf-1 kinase
    H Wang
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 273:16297-304. 1998
    14-3-3 proteins bind to a diverse group of regulatory molecules such as Raf-1, Cbl, and c-Bcr that are involved in signal transduction pathways...
  17. ncbi Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2
    C S Crovello
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 273:26954-61. 1998
    ..the EGF receptor, stimulating receptor tyrosine phosphorylation and the recruitment of phospholipase C-gamma, Cbl, SHP2, and Shc to that receptor...
  18. pmc An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis
    Gabi Tarcic
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Biol 19:1788-98. 2009
    ..from both the plasma membrane and from endosomes, and it is essential for recruitment of a ubiquitin ligase, CBL, that sorts activated receptors to endosomes and degradation...
  19. ncbi Cbl escapes Cdc42-mediated inhibition by downregulation of the adaptor molecule betaPix
    M H H Schmidt
    Institute of Biochemistry II, University Hospital of the Johann Wolfgang Goethe University, Frankfurt am Main, Germany
    Oncogene 25:3071-8. 2006
    ..Recently, it has been shown that betaPix/Cool-1 associates with the ubiquitin ligase Cbl, which appears to be a critical step in Cdc42-mediated inhibition of epidermal-growth-factor-receptor (EGFR) ..
  20. ncbi Epidermal growth factor receptor internalization through clathrin-coated pits requires Cbl RING finger and proline-rich domains but not receptor polyubiquitylation
    Xuejun Jiang
    Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80111, USA
    Traffic 4:529-43. 2003
    b>Cbl proteins have been implicated in the regulation of endocytic trafficking of epidermal growth factor receptor. However, the precise role of Cbl in epidermal growth factor receptor endocytosis is not defined...
  21. ncbi Cbl-mediated ubiquitinylation and negative regulation of Vav
    Yuko Miura-Shimura
    Division of Rheumatology, Immunology and Allergy, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:38495-504. 2003
    The Cbl ubiquitin ligase has emerged as a negative regulator of receptor and non-receptor tyrosine kinases...
  22. ncbi Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl
    Isabelle Gaston
    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Ore 97239, USA
    Exp Hematol 32:113-21. 2004
    b>Cbl is one of the major tyrosine-phosphorylated proteins in Bcr-Abl-expressing cells. A direct association between the SH2 domain of Bcr-Abl and tyrosine-phosphorylated Cbl has been demonstrated...
  23. ncbi A conserved DpYR motif in the juxtamembrane domain of the Met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation
    Pascal Peschard
    Department of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec H3A 1A1, Canada
    J Biol Chem 279:29565-71. 2004
    ..RTK) for hepatocyte growth factor, initiates the recruitment of multiple signaling proteins, one of which is c-Cbl, a ubiquitin-protein ligase...
  24. ncbi Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived growth factor receptor beta provides a dual mechanism of negative regulation
    Alagarsamy Lakku Reddi
    Division of Molecular Oncology, Evanston Northwestern Healthcare Research Institute, Northwestern University, Evanston, Illinois 60201, USA
    J Biol Chem 282:29336-47. 2007
    ..Our previous studies have established Cbl as an E3 ubiquitin ligase for ubiquitinylation and degradation of platelet-derived growth factor receptor (PDGFR) ..
  25. pmc Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism
    Margret S Fernandes
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Biol Chem 285:32596-605. 2010
    ..gain-of-function mutations in the α helical structure within the linker sequence of the E3 ubiquitin ligase CBL have been associated with AML...
  26. pmc Negative regulation of EGFR-Vav2 signaling axis by Cbl ubiquitin ligase controls EGF receptor-mediated epithelial cell adherens junction dynamics and cell migration
    Lei Duan
    Eppley Institute for Cancer and Allied Diseases, Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
    J Biol Chem 286:620-33. 2011
    The E3 ubiquitin ligase Casitas B lymphoma protein (Cbl) controls the ubiquitin-dependent degradation of EGF receptor (EGFR), but its role in regulating downstream signaling elements with which it associates and its impact on biological ..
  27. ncbi Dual phosphorylation of phosphoinositide 3-kinase adaptor Grb2-associated binder 2 is responsible for superoxide formation synergistically stimulated by Fc gamma and formyl-methionyl-leucyl-phenylalanine receptors in differentiated THP-1 cells
    Haruka Momose
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
    J Immunol 171:4227-34. 2003
    ..In this study, we identified two Tyr-phosphorylated proteins, c-Cbl (Casitas B-lineage lymphoma) and Grb2-associated binder 2 (Gab2), as PI 3-kinase adaptors that are Tyr ..
  28. ncbi Coupling of the c-Cbl protooncogene product to ErbB-1/EGF-receptor but not to other ErbB proteins
    G Levkowitz
    Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 12:1117-25. 1996
    ..are coupled to each ErbB protein, we examined the interaction of individual ligand-stimulated receptors with the c-Cbl protein, a protooncogene-encoded signaling molecule previously identified in hematopoietic cells...
  29. ncbi Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins
    D L Barber
    Ontario Cancer Institute, Division of Cellular and Molecular Biology, Toronto, Canada
    Blood 89:3166-74. 1997
    ..Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-..
  30. ncbi The linker phosphorylation site Tyr292 mediates the negative regulatory effect of Cbl on ZAP-70 in T cells
    N Rao
    Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 164:4616-26. 2000
    The protooncogene product Cbl has emerged as a negative regulator of tyrosine kinases. We have shown previously that Cbl binds to ZAP-70 through its N-terminal tyrosine kinase binding (TKB) domain...
  31. ncbi CIN85 associates with TNF receptor 1 via Src and modulates TNF-alpha-induced apoptosis
    Tadashi Narita
    Laboratory of Bacterial Infection and Immunity, Department of Immunology, National Institute of Infectious Diseases, 1 23 1, Toyama, Tokyo 162 8640, Japan
    Exp Cell Res 304:256-64. 2005
    ..However, CIN85 did not bind directly to the cytoplasmic domain of TNFR1 (TNFR1-CYT) but to Src family kinases, Cbl and the p85alpha subunit of phosphatidylinositol 3-kinase (PI3-K p85alpha)...
  32. ncbi Nef-mediated lipid raft exclusion of UbcH7 inhibits Cbl activity in T cells to positively regulate signaling
    Alison Simmons
    MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom
    Immunity 23:621-34. 2005
    ..Here, the E2 ubiquitin-conjugating enzyme UbcH7, which acts in conjunction with c-Cbl, is absent from lipid rafts...
  33. pmc Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation
    Feng Shen
    Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA
    Mol Biol Cell 18:732-42. 2007
    ..Taken together, our studies suggest that ACK1 senses signal of EGF and regulates ligand-induced degradation of EGFR...
  34. pmc Abi-1 forms an epidermal growth factor-inducible complex with Cbl: role in receptor endocytosis
    Barbara E Tanos
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cell Signal 19:1602-9. 2007
    ..Here we describe the identification of a novel complex between Abi-1 and the Cbl ubiquitin ligase that is induced by stimulation with EGF...
  35. ncbi The Cbl phosphotyrosine-binding domain selects a D(N/D)XpY motif and binds to the Tyr292 negative regulatory phosphorylation site of ZAP-70
    M L Lupher
    Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 272:33140-4. 1997
    The Cbl protooncogene product has emerged as a novel negative regulator of receptor and non-receptor tyrosine kinases through currently undefined mechanisms...
  36. ncbi cbl-b inhibits epidermal growth factor receptor signaling
    S A Ettenberg
    Genetics Department, Medicine Branch, National Cancer Institute, Bethesda Naval Hospital, Maryland 20889, USA
    Oncogene 18:1855-66. 1999
    The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR) was studied and compared with c-cbl...
  37. ncbi The c-Cbl/CD2AP complex regulates VEGF-induced endocytosis and degradation of Flt-1 (VEGFR-1)
    Satsuki Kobayashi
    Division of Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    FASEB J 18:929-31. 2004
    ..VEGF stimulation induced a ternary complex of Flt-1, c-Cbl, and CD2AP. Substitution of tyrosine 1333 in Flt-1 with phenylalanine (Y1333F) impaired its binding to c-Cbl...
  38. ncbi Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45
    Seiichi Okabe
    Department of Microbiology Immunology and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Blood Cells Mol Dis 36:308-14. 2006
    Stromal-cell-derived factor-1alpha (SDF-1alpha/CXCL12) is a potent chemoattractant for T cells. We report that Cbl family members, Cbl and Cbl-b, are tyrosine-phosphorylated after SDF-1alpha/CXCL12 stimulation of Jurkat T cells...
  39. ncbi The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif
    T J Blake
    Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, Australia
    Oncogene 6:653-7. 1991
    The murine Cas NS-1 retrovirus carries the v-cbl oncogene and induces pre-B cell lymphomas and myeloid leukemias...
  40. ncbi Physical association between Src homology 3 elements and the protein product of the c-cbl proto-oncogene
    O M Rivero-Lezcano
    Laboratory of Cellular Development and Oncology, NIDR, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 269:17363-6. 1994
    ..and one, designated SAKAP I (for Src A box Nck-associated protein I), contained the carboxyl-terminal half of the cbl proto-oncogene product...
  41. ncbi Tyrosine phosphorylation and translocation of the c-cbl protein after activation of tyrosine kinase signaling pathways
    S Tanaka
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 270:14347-51. 1995
    The c-cbl protooncogene product (c-Cbl) is a 120-kDa protein that has been shown to bind to the Src homology 3 domains of various proteins, suggesting its involvement in signal transduction pathways...
  42. ncbi The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor
    J A Donovan
    Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 269:22921-4. 1994
    ..This pathway has also been implicated in cellular transformation in multiple systems. The viral oncogene v-cbl is the transforming gene of a murine retrovirus that induces pre-B cell lymphomas and myelogenous leukemias...
  43. pmc Characterization of Cbl tyrosine phosphorylation and a Cbl-Syk complex in RBL-2H3 cells
    Y Ota
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 5430, USA
    J Exp Med 184:1713-23. 1996
    Tyrosine phosphorylation of the Cbl protooncogene has been shown to occur after engagement of a number of different receptors on hematopoietic cells...
  44. ncbi Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation
    C Heaney
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    Blood 89:297-306. 1997
    ..Thus, a direct interaction of CRKL and BCR-ABL is not required for CRKL to become tyrosine phosphorylated by BCR-ABL and suggests that CRKL function may still be required for BCR-ABL function through an indirect interaction...
  45. ncbi The Cbl family of signal transduction molecules
    L Smit
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam
    Crit Rev Oncog 8:359-79. 1997
    This review summarizes the current knowledge about the structure, expression, and signaling function of Cbl. A mutant Cbl form (v-Cbl) was first identified as the product of the Cas-NS-1 murine retrovirus that induces lymphomas and ..
  46. ncbi The c-Cbl oncoprotein
    M L Lupher
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Int J Biochem Cell Biol 30:439-44. 1998
    b>Cbl has emerged as a novel signal transducing protein downstream of a number of cell surface receptors coupled to tyrosine kinases...
  47. ncbi SLP-76-Cbl-Grb2-Shc interactions in FcgammaRI signaling
    J Chu
    Neil Bogart Memorial Laboratories, Division of Hematology Oncology, Childrens Hospital Los Angeles, Los Angeles, CA, USA
    Blood 92:1697-706. 1998
    SLP-76 and Cbl are complex adapter proteins that have the capacity to bind to smaller adapter proteins, such as Grb2, which subsequently binds the nucleotide exchange protein Sos in the transmission of intracellular signals...
  48. ncbi Activation of nuclear factor of activated T cells-(NFAT) and activating protein 1 (AP-1) by oncogenic 70Z Cbl requires an intact phosphotyrosine binding domain but not Crk(L) or p85 phosphatidylinositol 3-kinase association
    J E van Leeuwen
    Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 274:5153-62. 1999
    The Cbl proto-oncogene product is a complex adapter protein that functions as a negative regulator of protein tyrosine kinases...
  49. ncbi Cbl-mediated negative regulation of platelet-derived growth factor receptor-dependent cell proliferation. A critical role for Cbl tyrosine kinase-binding domain
    S Miyake
    Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 274:16619-28. 1999
    The Cbl proto-oncogene product has emerged as a novel negative regulator of receptor and non-receptor tyrosine kinases...
  50. ncbi Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling
    R K Park
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
    Blood 94:2112-20. 1999
    ..that FcalphaR-mediated signals modulate a multimolecular adaptor protein complex containing Grb2, Shc, SHIP, CrkL, Cbl, and SLP-76...
  51. ncbi The RING finger domain of Cbl is essential for negative regulation of the Syk tyrosine kinase
    S Ota
    Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 275:414-22. 2000
    The proto-oncogene product Cbl has emerged as a negative regulator of a number of protein-tyrosine kinases, including the ZAP-70/Syk tyrosine kinases that are critical for signaling in hematopoietic cells...
  52. ncbi The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction
    K H Kirsch
    Laboratory of Molecular Oncology, The Rockefeller University, New York, NY 10021, USA
    J Biol Chem 276:4957-63. 2001
    ..bound specifically to a tyrosine-phosphorylated protein of 120 kDa, which we identified as the proto-oncoprotein c-Cbl. The c-Cbl-binding site for CMS mapped to the carboxyl terminus of c-Cbl and is different from the proline-rich ..
  53. ncbi c-Cbl facilitates fibronectin matrix production by v-Abl-transformed NIH3T3 cells via activation of small GTPases
    A M Teckchandani
    Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania, PA 19140, USA
    Oncogene 20:1739-55. 2001
    The protooncogenic protein c-Cbl has been shown to act as a multivalent adaptor and a negative regulator of protein tyrosine kinase-mediated signaling. Recent studies have implicated it in the regulation of cell adhesion-related events...
  54. pmc Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking
    P Burke
    Department of Pathology, Division of Cell Biology and Immunology, University of Utah, Salt Lake City, Utah 84132, USA
    Mol Biol Cell 12:1897-910. 2001
    ..During the inactivation phase, c-Cbl became EGFR associated, consistent with its postulated role in receptor attenuation...
  55. ncbi The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met
    Annalisa Petrelli
    CNR CIOS and Department of Genetics, Biology and Biochemistry, University of Torino, 10126 Torino, Italy
    Nature 416:187-90. 2002
    ..Here we demonstrate that a complex involving endophilins, CIN85 and Cbl controls this process. Endophilins are regulatory components of clathrin-coated vesicle formation...
  56. ncbi Regulation of ubiquitin protein ligase activity in c-Cbl by phosphorylation-induced conformational change and constitutive activation by tyrosine to glutamate point mutations
    C Kenneth Kassenbrock
    Department of Pathology, University of Colorado Health Sciences Center, 4200 E Ninth Avenue, Denver, CO 80262, USA
    J Biol Chem 279:28017-27. 2004
    c-Cbl down-regulates receptor tyrosine kinases by conjugating ubiquitin to them, leading to receptor internalization and degradation...
  57. ncbi Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases
    Katarzyna Kowanetz
    Institute of Biochemistry II, Goethe University Medical School, 60590 Frankfurt, Germany
    J Biol Chem 279:32786-95. 2004
    The ubiquitin (Ub) ligase Cbl plays a critical role in attenuation of receptor tyrosine kinase (RTK) signaling by inducing ubiquitination of RTKs and promoting their sorting for endosomal degradation...
  58. pmc Growth factor receptor binding protein 2-mediated recruitment of the RING domain of Cbl to the epidermal growth factor receptor is essential and sufficient to support receptor endocytosis
    Fangtian Huang
    Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Mol Biol Cell 16:1268-81. 2005
    ..Overexpression of Grb2-binding protein c-Cbl did not restore endocytosis in Grb2-depleted cells...
  59. pmc Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia
    Michael A Caligiuri
    Integrated Biomeducal Graduate Program, Comprehensive Cancer Center, Ohio State University, Columbus, OH 23240, USA
    Blood 110:1022-4. 2007
    The CBL ubiquitin ligase targets a variety of activated tyrosine kinases (TKs) for degradation. Many TKs are mutationally or autocrine activated and/or often overexpressed at the mRNA and protein levels in acute leukemias...
  60. ncbi Structural basis for UBA-mediated dimerization of c-Cbl ubiquitin ligase
    Guennadi Kozlov
    Departments of Biochemistry, Medicine, and Oncology, McGill University, Molecular Oncology Group, McGill University Health Center, Montreal, Quebec, Canada
    J Biol Chem 282:27547-55. 2007
    Ligand-induced down-regulation by the ubiquitin-protein ligases, c-Cbl and Cbl-b, controls signaling downstream from many receptor-tyrosine kinases (RTK)...
  61. doi CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes
    Carola Reindl
    Department of Medicine III, University Hospital Grosshadern, Ludwig Maximilians University, Helmholtz Center Munich, Munich, Germany
    Clin Cancer Res 15:2238-47. 2009
    b>CBL is a negative regulator of activated receptor tyrosine kinases (RTK). In this study, we determined the frequency of CBL mutations in acute leukemias and evaluated the oncogenic potential of mutant CBL.
  62. doi Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms
    Francis H Grand
    Wessex Regional Genetics Laboratory, Salisbury, United Kingdom
    Blood 113:6182-92. 2009
    ..In total, 7 different chromosomes were involved with 7q and 11q each affected in 10% of aCML cases. CBL mutations were identified in all 3 cases with 11q aUPD and analysis of 574 additional MPNs revealed a total of 27 ..
  63. doi CIN85 associates with endosomal membrane and binds phosphatidic acid
    Jing Zhang
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Cell Res 19:733-46. 2009
    CIN85 (Cbl-interacting protein of 85 kDa) is an important molecule involved in receptor tyrosine kinase endocytosis...
  64. pmc Mutations in CBL occur frequently in juvenile myelomonocytic leukemia
    Mignon L Loh
    Department of Pediatrics and the Comprehensive Cancer Center, University of California, San Francisco, California, USA
    Blood 114:1859-63. 2009
    ..Using single nucleotide polymorphism arrays, we identified a region of 11q isodisomy that contains the CBL gene in several JMML samples, and subsequently identified CBL mutations in 27 of 159 JMML samples...
  65. pmc Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia
    Hideki Muramatsu
    Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, OH 44195, USA
    Blood 115:1969-75. 2010
    ..somatic uniparental disomy 11q was detected in 4 of 49 patients; all of these cases harbored RING finger domain c-Cbl mutations. In total, c-Cbl mutations were detected in 5 (10%) of 49 patients...
  66. doi Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies
    Ulrike Bacher
    Interdisciplinary Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Martinistr 52, 20246 Hamburg, Germany
    Ann Hematol 89:643-52. 2010
    ..Recently, mutations of the tet oncogene family member 2 (TET2) and Casitas B-cell lymphoma (CBL) genes became the focus of interest...
  67. pmc A Dyn2-CIN85 complex mediates degradative traffic of the EGFR by regulation of late endosomal budding
    Barbara Schroeder
    Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
    EMBO J 29:3039-53. 2010
    ..The adaptor protein CIN85 (cbl-interacting protein of 85 kDa), which has been proposed to indirectly link the EGFR to the endocytic machinery at ..
  68. pmc Kaposi's sarcoma-associated herpesvirus interacts with EphrinA2 receptor to amplify signaling essential for productive infection
    Sayan Chakraborty
    H M Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA
    Proc Natl Acad Sci U S A 109:E1163-72. 2012
    ..KSHV infection activated c-Cbl, which induced the selective translocation of KSHV into lipid rafts (LRs) along with the α3β1, αVβ3, and xCT ..
  69. ncbi The proto-oncogene product c-Cbl becomes tyrosine phosphorylated by stimulation with GM-CSF or Epo and constitutively binds to the SH3 domain of Grb2/Ash in human hematopoietic cells
    H Odai
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
    J Biol Chem 270:10800-5. 1995
    ..from the in situ protease digestion of the purified pp130 showed that the pp130 was identical to the human c-cbl proto-oncogene product (c-Cbl)...
  70. ncbi Coupling of the proto-oncogene product c-Cbl to the epidermal growth factor receptor
    H Meisner
    Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605, USA
    J Biol Chem 270:25332-5. 1995
    The proto-oncogene product, Cbl, is a 120-kDa protein present in lymphocytes that contains numerous PXXP motifs in its COOH-terminal region and constitutively binds the SH3-containing adaptor protein Grb2...
  71. pmc The protein product of the c-cbl protooncogene is phosphorylated after B cell receptor stimulation and binds the SH3 domain of Bruton's tyrosine kinase
    G O Cory
    Molecular Immunology Unit, University of London, United Kingdom
    J Exp Med 182:611-5. 1995
    ..We have shown that this 120-kD protein is the protein product of c-cbl, a protooncogene, which is known to be phosphorylated in response to T cell receptor stimulation and to interact ..
  72. ncbi Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation
    M L Galisteo
    Department of Pharmacology, New York University Medical Center, New York 10016, USA
    J Biol Chem 270:20242-5. 1995
    The murine retroviral oncogene v-cbl induces pre-B cell lymphomas and myelogenous leukemias...
  73. ncbi Identification of the major tyrosine kinase substrate in signaling complexes formed after engagement of Fc gamma receptors
    A Marcilla
    Laboratory of Cellular Development and Oncology, NIDR, National Institutes of Health, Bethesda, Maryland 20892 4330, USA
    J Biol Chem 270:9115-20. 1995
    We have recently identified the protein product of the c-cbl proto-oncogene as an SH3 binding protein expressed in macrophages...
  74. ncbi Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fc gamma receptor signaling
    T Matsuo
    Ui Laboratory, Institute of Physical and Chemical Research, Wako Shi, Japan
    FEBS Lett 382:11-4. 1996
    ..1994) J. Biol. Chem. 269, 22732-22737]. Here, the 115-kDa protein is identified as the product of human c-cbl protooncogene...
  75. ncbi p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase
    G Panchamoorthy
    Lymphocyte Biology Section, Division of Rheumatology and Immunology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:3187-94. 1996
    We and others have demonstrated that the c-cbl proto-oncogene product is one of the earliest targets of tyrosine phosphorylation upon T cell receptor stimulation...
  76. ncbi Tyrosine phosphorylation of Cbl upon epidermal growth factor (EGF) stimulation and its association with EGF receptor and downstream signaling proteins
    T Fukazawa
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:14554-9. 1996
    We and others have shown that Cbl, the protein product of the c-cbl proto-oncogene, is an early target of tyrosine phosphorylation upon stimulation through the immune cell surface receptors, which signal through noncovalently associated ..
  77. pmc ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling
    D Graus-Porta
    Friedrich Miescher Institute, Basel, Switzerland
    EMBO J 16:1647-55. 1997
    ..BTC and NDF) couples to SHC, whereas only ErbB-1 activated by its own ligands associates with and phosphorylates Cbl. These results provide the first biochemical evidence that a given ErbB receptor has distinct signaling properties ..
  78. ncbi Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells
    A Bhat
    Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 97201, USA
    J Biol Chem 272:16170-5. 1997
    ..In this study we mapped a direct binding site of the c-CBL proto-oncogene to the SH2 domain of BCR-ABL...
  79. ncbi Maintenance of human T cell anergy: blocking of IL-2 gene transcription by activated Rap1
    V A Boussiotis
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 278:124-8. 1997
    ..Anergic alloantigen-specific human T cells contained phosphorylated Cbl that coimmunoprecipitated with Fyn...
  80. ncbi Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases
    M Deckert
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 273:8867-74. 1998
    ..b>Cbl is a prominent PTK substrate suggesting a pivotal role for it in early signal transduction events...
  81. ncbi Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl
    L J Graham
    Division of Monoclonal Antibodies, US Food and Drug Administration, Bethesda, Maryland, 20852, USA
    Biochem Biophys Res Commun 249:537-41. 1998
    SH3 domains are protein modules that interact with proline-rich polypeptide fragments. Cbl is an adapter-like protein known to interact with several SH3 domains, including the PLCgamma1 SH3 domain and the Grb2 amino terminal SH3 domain...
  82. ncbi Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323
    M L Lupher
    Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 273:35273-81. 1998
    The proto-oncogene product Cbl has emerged as a potential negative regulator of the Syk tyrosine kinase; however, the nature of physical interactions between Cbl and Syk that are critical for this negative regulation remains unclear...
  83. ncbi Dual regulation of T cell receptor-mediated signaling by oncogenic Cbl mutant 70Z
    Z Zhang
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    J Biol Chem 274:4883-9. 1999
    We previously showed that an oncogenic Cbl mutant (70Z) is constitutively active in transcriptional activation of nuclear factor at activated T cells (NFAT). However, the mechanism underlying this effect remains unclear...
  84. ncbi Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase
    W Meng
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 398:84-90. 1999
    b>Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface...
  85. ncbi Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages
    A Erdreich-Epstein
    Neil Bogart Memorial Laboratories, Department of Pediatrics, Childrens Hospital Los Angeles Research Institute, University of Southern California School of Medicine, USA
    J Leukoc Biol 65:523-34. 1999
    b>Cbl is a cytosolic protein that is rapidly tyrosine phosphorylated in response to Fc receptor activation and binds to the adaptor proteins Grb2, CrkL, and Nck. A few reports describe Cbl interactions in primary human hematopoietic cells...
  86. ncbi The RING finger of c-Cbl mediates desensitization of the epidermal growth factor receptor
    H Waterman
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 274:22151-4. 1999
    ..c-Cbl, a tyrosine phosphorylation substrate shared by several signaling pathways, accelerates desensitization by ..
  87. ncbi Leucine zipper-mediated homodimerization of the adaptor protein c-Cbl. A role in c-Cbl's tyrosine phosphorylation and its association with epidermal growth factor receptor
    M Bartkiewicz
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 274:30887-95. 1999
    The 120-kDa proto-oncogenic protein c-Cbl is a multidomain adaptor protein that is phosphorylated in response to the stimulation of a broad range of cell surface receptors and participates in the assembly of signaling complexes that are ..
  88. ncbi Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7
    M Yokouchi
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 274:31707-12. 1999
    c-Cbl plays a negative regulatory role in tyrosine kinase signaling by an as yet undefined mechanism...
  89. ncbi Role of Syk in Fc gamma receptor-coupled tyrosine phosphorylation of Cbl in a manner susceptible to inhibition by protein kinase C
    K Hazeki
    The Ui Laboratory Institute of Physical and Chemical Research, Wako Shi, Japan
    Eur J Immunol 29:3302-12. 1999
    Fcgamma receptors (FcgammaR) of guinea pig neutrophils were ligated and anti-Cbl immunoprecipitates prepared therefrom were assayed for the associated protein tyrosine kinase activity, which increased upon ligation of FcgammaR...
  90. pmc The Cbl proto-oncogene product negatively regulates the Src-family tyrosine kinase Fyn by enhancing its degradation
    C E Andoniou
    Lymphocyte Biology Section, Division of Rheumatology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 20:851-67. 2000
    ..We have investigated the possibility that the tyrosine kinase regulatory protein Cbl provides a complementary mechanism of Fyn regulation...
  91. ncbi Evidence for direct interaction between Sprouty and Cbl
    E S Wong
    Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, Singapore 117609, Singapore
    J Biol Chem 276:5866-75. 2001
    ..Here, we demonstrate that hSPRY2 associates directly with c-Cbl, a known down-regulator of RTK signaling...
  92. ncbi Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors
    Philippe Soubeyran
    Ludwig Institute for Cancer Research, Box 595, Husargatan 3, Uppsala, S 75124, Sweden
    Nature 416:183-7. 2002
    b>Cbl is a multi-adaptor protein involved in ligand-induced downregulation of receptor tyrosine kinases...
  93. ncbi SHP-1 regulates Fcgamma receptor-mediated phagocytosis and the activation of RAC
    Anita M Kant
    Herman B Wells Center for Pediatrics Research, Indiana University School of Medicine, Indianapolis 46202, USA
    Blood 100:1852-9. 2002
    ..Stimulation with sensitized sheep red blood cells (sRBCs) induced tyrosine phosphorylation of CBL and association of CBL with CRKL...
  94. pmc Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling
    Esther Sook Miin Wong
    Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Drive, Singapore 117609
    EMBO J 21:4796-808. 2002
    ..herein that describes the functional implications of the direct association between human Sprouty2 (hSpry2) and c-Cbl, and its impact on the cellular localization and signalling capacity of EGFR...
  95. ncbi Sprouty fine-tunes EGF signaling through interlinked positive and negative feedback loops
    Chanan Rubin
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Biol 13:297-307. 2003
    ..c-Cbl is an adaptor that modulates this process by recruiting binding partners, such as ubiquitin-conjugating enzymes...
  96. ncbi CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment, but elicit divergent functional activities
    Elena V Tibaldi
    Laboratory of Immunobiology, Dana Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Int Immunol 15:313-29. 2003
    ..CIN85/CD2BP3 themselves as evidenced by mAb accessibility analysis and protein interaction studies including c-Cbl binding. This form of intramolecular regulation is not manifest by CMS...
  97. ncbi SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion
    Mirko H H Schmidt
    William and Karen Davidson Laboratory of Brain Tumor Biology, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202, USA
    J Cell Sci 116:2845-55. 2003
    ..regulating diverse signal transduction pathways, including the internalization of tyrosine kinase receptors via the Cbl ubiquitin ligases, and attenuating PI3K activity by interaction with its regulatory subunit...
  98. ncbi Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function
    Chee Wai Fong
    Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, Singapore, 117609 Singapore
    J Biol Chem 278:33456-64. 2003
    ..that hSpry2 is tyrosine-phosphorylated upon stimulation by either FGFR or EGF and subsequently binds endogenous c-Cbl with high affinity...
  99. ncbi Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors
    Katarzyna Kowanetz
    Institute of Biochemistry II, University of Frankfurt Medical School, Theodor Stern Kai 7, Frankfurt 60590, Germany
    J Biol Chem 278:39735-46. 2003
    CIN85 is a multidomain adaptor protein implicated in Cbl-mediated down-regulation of receptor tyrosine kinases...
  100. ncbi Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation
    Wen Jin Wu
    Department of Molecular Medicine, Veterinary Medical Center, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA
    Cell 114:715-25. 2003
    ..Here, we show that activation of Cdc42 protects the EGF receptor from the negative regulatory activity of the c-Cbl ubiquitin ligase...
  101. ncbi Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl)
    Shan Zeng
    Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Blood 105:226-32. 2005
    ..Here, we show that stem cell factor (SCF), the ligand for KIT, induces the interaction between KIT and Cbl proteins and their mutual degradation...

Research Grants64

  1. Novel TIRF microscopy analyzing trafficking & signaling at the cell cortex
    Derek Toomre; Fiscal Year: 2009
    ..Consistent with the recovery act's goal, this funding will provide full-time summer employment for 4 undergraduate students and accelerate scientific achievement of the parent DP2 award...
  2. Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte Death
    Abdelkarim Sabri; Fiscal Year: 2012
    ..The proto-oncogene Casitas b-lineage lymphoma (Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor tyrosine kinase ..
  3. Mitchell Kronenberg; Fiscal Year: 2014
    ..In Project 1, led by Dr. Liu, we will investigate how an E3 ubiquitin ligase, Cbl-b, stimulates Foxp3 induction, via a pathway that leads to increased activity of the transcription factor Foxo3a...
  4. Scavenging of Reactive Oxygen and Nitrogen Species by Cobalamins
    NICOLA ELIZABETH BRASCH; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Cobalamins (Cbl, vitamin B12 derivatives) are essential cofactors in mammals. However, they also have clinical effects that cannot be fully explained solely by their cofactor role...
  5. The Transcobalamin Receptor in Cobalamin Homeostasis
    Edward V Quadros; Fiscal Year: 2011
    Vitamin B12 (cobalamin, Cbl) deficiency in humans produces megaloblastic anemia and neuropathologic disorders...
  6. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
    ..By sequencing the c-Cbl gene, an E3 ubiquitin ligase in this chromosomal region, a mutation involving a critical part of this gene was ..
  7. Jordan A Kreidberg; Fiscal Year: 2014
    ..Failure to ubquitinate c-Met is due to sequestration of the E3 ubiquitin ligase c-Cbl by 31 integrin in the Golgi apparatus...
  8. GDNF and Ret are critical for glomerular development, maintenance, and protection
    CYNTHIA TSUI; Fiscal Year: 2013
    ..vivo, and that the administration of exogenous GDNF is a therapeutic intervention, and (3) test the hypothesis that Cbl- 3 is the E3-ligase controlled by CD2AP that is responsible for Ret degradation and signaling...
  9. JENNIFER LYNN STRIPAY; Fiscal Year: 2015
    ..Previous work [13] has identified a novel regulatory pathway (the redox/Fyn/c-Cbl (RFC)) pathway that is present in progenitor cells of the CNS, and appears to be dysregulated in GBM...
  10. SPRY2 predicts survival post-chemotherapy in advanced ovarian cancer.
    Raymond P Perez; Fiscal Year: 2010
    ..Many of its actions depend on a dynamic equilibrium with Cbl, an E3-ligase that targets SPRY2 as well as EGF-family receptors for proteosomal degradation...
  11. Jaroslaw P Maciejewski; Fiscal Year: 2014
    ..Sequencing of this region demonstrated mutations in c-Cbl, an E3 ubiquitin ligase...
  12. Vascular Biochemistry of Vitamin B12
    DONALD JACOBSEN; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): The micronutrient B12 (cobalamin, Cbl) plays an essential role in homocysteine metabolism in most if not all cells in the body...
  13. Regulation of Osteoclast Function : Role of the Cbl-PI3K Complex
    Archana Sanjay; Fiscal Year: 2012
    ..Our preliminary data has shown that in osteoclasts, deletion of cbl gene impairs osteoclast migration during development...
  14. Mechanism of Pseudomonas-mediated epithelial cell damage
    Joanne N Engel; Fiscal Year: 2010
    ..We have discovered that Cbl-b, an adaptor molecule with E3 ubiquitin ligase activity modulates the stability of ExoT by targeted proteasomal ..
  15. Nitrosylcobalamin - A Novel Chemotherapeutic Agent
    Daniel Lindner; Fiscal Year: 2007
    ..DESCRIPTION (provided by applicant): Through receptor-mediated uptake and nitric oxide release, nitrosylcobalamin (NO-Cbl) was designed to induce cell death in malignancies with high requirement for cobalamin...
  16. Molecular screen for isopeptidase inhibitors to treat pulmonary disease
    David E Sterner; Fiscal Year: 2011
    ..An alternative ubiquitin-associated degradation pathway is lysosomal;for example, the ubiquitin E3 ligase Cbl promotes degradation of membrane bound epithelial growth factor receptor (EGFR) by ubiquitylating the receptor, ..
  17. Hening Lin; Fiscal Year: 2016
    ..when activated by certain ligands, CD38 can trigger the phosphorylation of intracellular proteins, including c-Cbl and mitogen-activated protein kinases (MAPK)...
  18. Kenneth S K Tung; Fiscal Year: 2016
    ..discovered that the Teff cells of B6AF1-DEREG mice with AO resist Treg suppression, and they express low levels Cbl-b. Cbl-b is an E3 ligase the controls the TCR response threshold...
  19. Khadija Rafiq; Fiscal Year: 2016
    ..myocytes with ISPs led to IR/IGF-1R ubiquitylation and degradation through activation of E3 ubiquitin ligase Cbl and ubiquitin proteasome system (UPS), respectively...
  20. Nedd4-family ubiquitination networks that regulate T cell function
    PAULA MARIA OLIVER; Fiscal Year: 2012
    ..We have found that Nedd4 promotes T cell activation by decreasing levels of Cbl-b...
  21. B Cell Receptor Regulation of Antigen Processing
    MARCUS CLARK; Fiscal Year: 2009
    ..Farther downstream, the ubiquitin ligase Cbl-b is required for entry into the antigen processing compartments...
  22. A NANOPARTICLE CD8 T CELL REGIMEN FOR CANCER THERAPY
    Jian Li; Fiscal Year: 2009
    ..Recent studies by us and others have identified that CD8+ T cells ablated Cbl-b, a member of ubiquitin E3 ligase family, may overcome such an obstacle and thus provide a novel target for ..
  23. The role of CAP in macrophage function
    Nicole M White; Fiscal Year: 2010
    ..the function of macrophages in metabolic disease pathology by specifically focusing on the function of Cbl-associated protein (CAP) in macrophages...
  24. Survival and growth-promotion mechanisms of the GDNF family ligands (GFLs)
    BRIAN ANTHONY PIERCHALA; Fiscal Year: 2012
    ..augments Ret activation via the inhibition of the activity-dependent degradation of Ret through the modulation of Cbl-3 and CD2AP, two important regulators of receptor tyrosine kinases...
  25. MOLECULAR CONTROL OF EGF RECEPTOR DOWN-REGULATION
    Hamid Band; Fiscal Year: 2012
    ..We and others have established that Cbl-family ubiquitin ligase proteins play a crucial role in EGFR down-regulation by faciliatating receptor ..
  26. White matter damage in Alzheimer?s disease: New cellular targets and mechanisms
    Mark Noble; Fiscal Year: 2009
    ..This leads to activation of c-Cbl, an E3 ubiquitin ligase that is a target of Fyn...
  27. Hamid Band; Fiscal Year: 2014
    ..We, and others, have shown that Cbl family of ubiquitin ligases are essential regulators of the lysosomal fate...
  28. Richard A Cerione; Fiscal Year: 2016
    ..One involves EGFR-signaling through the small GTPase Cdc42 that regulates EGFR-Cbl interactions and EGFR degradation, whereas the second pathway links HRG-signaling through the small GTPase Rac to ..
  29. CNS vulnerability to systemic chemotherapy: Causes and prevention
    Mark D Noble; Fiscal Year: 2012
    ..of primary cells -but not cancer cells - by convergence on a newly discovered regulatory pathway (the redox/Fyn/c-Cbl pathway) that converts small increases in oxidative state into enhanced degradation of a subset of receptor ..
  30. George J Schwartz; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The Central Biochemistry Laboratory (CBL) serves the subjects and investigators of the continuing Prospective Study of Chronic Kidney Disease in Children (CKiD)...
  31. Hamid Band; Fiscal Year: 2015
    ..Studies by the PI and others have established the Cbl family of ubiquitin ligases (E3s) as physiological negative regulators of PTK signaling...
  32. Joel S Bennett; Fiscal Year: 2016
    ..platelet signaling responses to immune complex/Fc?RIIA interactions, focusing on the tyrosine kinase syk and the cbl family of adaptors/E3 ubiquitin ligases, and will make use of unique transgenic and knockout mouse lines...
  33. Haifeng Yang; Fiscal Year: 2016
    ..This proposal will investigate how pVHL antagonizes EGFR through multiple mechanisms: a) promoting c-Cbl-independent poly-ubiquitylation and degradation of activated EGFR;b) affecting EGFR signaling transcriptionally by ..
  34. Ronald M Evans; Fiscal Year: 2016
    ..properties of PPARd epi-genomic complexes assembled in the presence of two selective modulators GW1516 and Syndag CBL-28...
  35. Regulation of the Endocytic Trafficking of CFTR
    Agnieszka Swiatecka-Urban; Fiscal Year: 2012
    ..Specific Aim #2. Test the hypothesis that c-Cbl inhibits the expression of CFTR in the apical membrane by facilitating CFTR endocytosis in airway epithelial cells...
  36. DISSECTION OF THE FUNCTIONS OF HERPES SIMPLEX VIRUS ICPO
    Bernard Roizman; Fiscal Year: 2012
    ..This led to a fundamental discovery that the virus targets surface receptors in many different ways. CIN85 and Cbl are blocked from cycling to the cell surface...
  37. Brain Cannabinoid Signaling: Selectivity and Adaptation
    Laura J Sim Selley; Fiscal Year: 2010
    ..THC), the psychoactive component of marijuana, produces a variety of effects by activating cannaibinoid CBl receptors (CB1R) in specific CNS regions...
  38. FUNCTIONAL DISSECTION OF CBLS TRANSFORMING DOMAIN
    Hamid Band; Fiscal Year: 2002
    ..Biochemical studies from Dr. Band's laboratory and independent genetic studies in C. elegans have identified the c-cbl proto-oncogene product as a potential regulator of tyrosine kinase signaling...
  39. Mechanisms of colon cancer chemoprevention by ursodeoxycholic acid
    Jesse D Martinez; Fiscal Year: 2013
    ..to be involved in silencing of activated receptors through endocytosis which is followed by ubiquitination by c-Cbl and degradation...
  40. CBL PROTOONCOGENE SIGNALING MECHANISMS
    LAURIE BEITZ; Fiscal Year: 2001
    ..demonstrated that activation of these receptors induces SRC family kinases and SYK to physically interact with the CBL proto-oncogene to form CBL/kinase complexes...
  41. C CBL IN MODULATION OF CELL ADHESION AND MORPHOLOGY
    Alexander Tsygankov; Fiscal Year: 2005
    DESCRIPTION: (Adapted from the investigator's abstract) The protooncogenic protein c-Cbl is tyrosine phosphorylated both in normal cells in response to various stimuli and in cells transformed by oncogenic protein tyrosine kinases (PTKs)..
  42. Enhancement of Dendritic Cells for Improved Immunotherapy
    David Spencer; Fiscal Year: 2009
    ..temporally controlled DC-specific activation within the context of an immunological synapse, downregulation of c-Cbl in DCs to stabilize endogenous CD40 expression following ligand binding, and development of an "optimized" lipid ..
  43. Andrew Yen; Fiscal Year: 2015
    ..3) CD38 has a cytosolic tail capable of binding to MAPK signaling molecules, in particular the c-Cbl adaptor...
  44. Molecular screen for isopeptidase inhibitors to treat pulmonary disease
    DAVID STERNER; Fiscal Year: 2007
    ..The ubiquitin E3 ligase Cbl promotes the ubiquitination and sorting of the EGFR to late endosomes and lysosomes, where it is degraded by acidic ..
  45. Jian Zhang; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Casitas-B-lineage lymphoma protein-b (Cbl-b) is an adaptor protein and RING finger domain-type E3 ubiquitin (Ub) ligase, and has been shown to be important for the maintenance of a balance between ..
  46. Enhancing CD8 T Cell Function by Abrogating Inhibition by Regulatory Proteins
    Joseph N Blattman; Fiscal Year: 2010
    ..We have identified Cbl-b, SHP-1, and SOCS-1 as potential targets to enhance CDS T cell aviditiy and function...
  47. AN INSTITUTIONAL NRSA IN MOLECULAR BIOPHYSICS
    CLAUDIO F GROSMAN; Fiscal Year: 2013
    ..and career advising, provided jointly with the Cell &Molecular Biology (CMB) and Chemistry-Biology Interface (CBl) training grants. Ten traineeship stipends are requested, generally to be provided in years 2-3...
  48. A Novel Therapeutic for Chronic Kidney Disease
    Prakash Narayan; Fiscal Year: 2010
    ..NY and Chemical and Biopharmaceutical Laboratories (CBL, CO) have developed a library of H2R-like peptides in commercially viable quantities at a fraction of the cost ..
  49. The Transcobalamin Receptor in Cobalamin Homeostasis
    Edward V Quadros; Fiscal Year: 2010
    The essential role of vitamin B12 (Cbl) in recycling folate and thereby in DMA synthesis and single carbon metabolism and in the generation of methionine, the precursor for biological methylations is indicated by the clinical ..
  50. Engineering intrabodies for knockdown of target proteins in cancer cells
    Amy J Karlsson; Fiscal Year: 2011
    ..The intrabodies will target CD38 and c-Cbl, proteins that have critical roles in MAPK signaling. Following screening of intrabodies displayed on the E...
  51. A Novel Therapeutic for Liver Fibrosis
    Prakash Narayan; Fiscal Year: 2011
    ..NY and Chemical and Biopharmaceutical Laboratories (CBL, CO) have developed a library of H2R-like peptides in commercially viable quantities at a fraction of the cost ..
  52. Bala Chandran; Fiscal Year: 2016
    ..We have also demonstrated that c-Cbl play a role in KSHV macropinocytosis...
  53. Understanding intellectual disability in Noonan syndrome and related disorders
    Bruce D Gelb; Fiscal Year: 2013
    ..e., CBL, SHP2, SOS, RAS, RAF and MEK proteins)...
  54. Jon C D Houtman; Fiscal Year: 2014
    ..we will 1) molecularly characterize the interaction of Grb2 with the SH3 domain ligands Sos1, HPK1 and c-Cbl, 2) determine the forces that drive the association of specific Grb2 SH3 domain ligands with LAT and 3) determine ..
  55. NICOLE JANET SCOTT; Fiscal Year: 2014
    ..that physiologically relevant concentrations of psychosine are activating the previously described [13] redox/Fyn/c-Cbl pathway in primary oligodendrocyte/type-2 astrocyte progenitor cells (O-2A/OPCs)...
  56. Yun Cai Liu; Fiscal Year: 2015
    ..Particularly, we have studied two critical E3 ligases Itch and Cbl-b in immune regulation and have made significant progress during the current funding period, which establish these ..
  57. Michael J Mugavero; Fiscal Year: 2016
    ..to screen positive will receive either another session of CBI or will be offered CBI and alcohol pharmacotheray (CBl+APT)...
  58. SHEAR STRESS ENHANCEMENT OF SMOOTH MUSCLE CELL MIGRATION
    John Shyy; Fiscal Year: 2003
    ..Preliminary studies with use of flow channel show that the Cbl, which is a proto-oncogene product (Sasitas B-lineage lymphoma), and is the cellular homology of the alcoprotein b-..
  59. ROLE OF THE C-SRC PROTO-ONCOGENE IN OSTEOCLASTS
    Roland Baron; Fiscal Year: 2009
    ..is the molecular basis for Src's "uniqueness" in osteoclast function? and 2/ Why would the phosphorylation of Cbl be so important in the osteoclast? For the next funding period, we propose to 1) identify the molecular basis for ..
  60. Effects of the Angiopoietins on Tie 2 Downregulation
    Christopher Kontos; Fiscal Year: 2005
    ..in a ubiquitin-dependent fashion, and in most cases this process is mediated by the E3 ubiquitin ligase c-Cbl, c-Cbl can associate directly with activated RTKs, whereupon it effects receptor ubiquitination, internalization, ..
  61. PDGF Receptor Regulation by CBL
    Hamid Band; Fiscal Year: 2007
    ..Our recent work has established the Cbl proto-oncoprotein as a crucial regulator of PDGF receptor down-regulation...
  62. Ramesh K Ganju; Fiscal Year: 2016
    ..a key regulatory signaling molecule linked to CXCR4-mediated breast cancer cell chemotaxis and chemoinvasion is Cbl. The first specific aim of this proposal is to characterize the interaction between Cbl and the CXCR4 receptor...
  63. Thrombin,Sepsis and Mechanisms of Inflammation
    Chinnaswamy Tiruppathi; Fiscal Year: 2010
    ..In addition, we show Supporting Data that in ubiquitin ligase Cbl-b-null (Cbl-b"'") mice, PAR-1 agonist-induced Ca2+ influx and increased lung vascular permeability were ..
  64. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford Lowell; Fiscal Year: 2005
    ..This integrin signaling pathway involves the adapter protein c-Cbl and the lipid kinase PI-3 kinase...