src family kinases

Summary

Summary: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.

Top Publications

  1. ncbi Src family kinases in tumor progression and metastasis
    Justin M Summy
    The University of Texas M D Anderson Cancer Center, Department of Cancer Biology, Houston, TX 77030, USA
    Cancer Metastasis Rev 22:337-58. 2003
  2. ncbi FAK integrates growth-factor and integrin signals to promote cell migration
    D J Sieg
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nat Cell Biol 2:249-56. 2000
  3. ncbi The interplay between Src and integrins in normal and tumor biology
    Martin P Playford
    Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Oncogene 23:7928-46. 2004
  4. ncbi Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex
    Yasuyuki Fujita
    Max Delbruck Center for Molecular Medicine, Robert Rossle Str 10, 13125 Berlin, Germany
    Nat Cell Biol 4:222-31. 2002
  5. ncbi Src in cancer: deregulation and consequences for cell behaviour
    Margaret C Frame
    The Beatson Institute for Cancer Research and Institute of Biomedical and Life Sciences, CRC Beatson Laboratories University of Glasgow, Glasgow, UK
    Biochim Biophys Acta 1602:114-30. 2002
  6. ncbi Integrin-regulated FAK-Src signaling in normal and cancer cells
    Satyajit K Mitra
    The Scripps Research Institute, Department of Immunology, IMM21 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 18:516-23. 2006
  7. pmc HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction
    Ronald P Trible
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:27029-38. 2006
  8. ncbi Ras signalling on the endoplasmic reticulum and the Golgi
    Vi K Chiu
    Department of Medicine, Cell Biology and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Nat Cell Biol 4:343-50. 2002
  9. ncbi Structure and regulation of Src family kinases
    Titus J Boggon
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Oncogene 23:7918-27. 2004
  10. pmc The Src family tyrosine kinase Fyn regulates natural killer T cell development
    P Gadue
    Graduate Program in Immunology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Exp Med 190:1189-96. 1999

Research Grants

  1. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford A Lowell; Fiscal Year: 2013
  2. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
  3. Regulation of Signaling Receptor Activity by LRP-1
    Steven L Gonias; Fiscal Year: 2013
  4. Innate and Adaptive Immune Mechanisms in Arthritis
    RICHARD J BUCALA; Fiscal Year: 2013
  5. Mechanisms of pox virus motility and release
    Daniel Kalman; Fiscal Year: 2012
  6. INTEGRIN SIGNALING IN HEMOSTASIS AND BLOOD DISEASES
    Sanford J Shattil; Fiscal Year: 2012
  7. Novel Strategy for Lung Cancer Treatment Using IGF-1R Inhibitor
    Ho Young Lee; Fiscal Year: 2013
  8. Cadherin-catenin Mediated Contact Inhibition of Cell Growth
    Barry M Gumbiner; Fiscal Year: 2013
  9. Tau in cancer cells
    Gloria Lee; Fiscal Year: 2010
  10. Regulation of the hematopoietic-cell transmembrane phosphatases CD45 and CD148
    Tanya S Freedman; Fiscal Year: 2010

Detail Information

Publications345 found, 100 shown here

  1. ncbi Src family kinases in tumor progression and metastasis
    Justin M Summy
    The University of Texas M D Anderson Cancer Center, Department of Cancer Biology, Houston, TX 77030, USA
    Cancer Metastasis Rev 22:337-58. 2003
    ..Constitutively activated variants of Src family kinases, including the viral oncoproteins v-Src and v-Yes, are capable of inducing malignant transformation of a ..
  2. ncbi FAK integrates growth-factor and integrin signals to promote cell migration
    D J Sieg
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Nat Cell Biol 2:249-56. 2000
    ..Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways...
  3. ncbi The interplay between Src and integrins in normal and tumor biology
    Martin P Playford
    Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Oncogene 23:7928-46. 2004
    ....
  4. ncbi Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex
    Yasuyuki Fujita
    Max Delbruck Center for Molecular Medicine, Robert Rossle Str 10, 13125 Berlin, Germany
    Nat Cell Biol 4:222-31. 2002
    ..Through dynamic recycling of E-cadherin, Hakai can thus modulate cell adhesion, and could participate in the regulation of epithelial--mesenchymal transitions in development or metastasis...
  5. ncbi Src in cancer: deregulation and consequences for cell behaviour
    Margaret C Frame
    The Beatson Institute for Cancer Research and Institute of Biomedical and Life Sciences, CRC Beatson Laboratories University of Glasgow, Glasgow, UK
    Biochim Biophys Acta 1602:114-30. 2002
    ..Consequently, there is optimism that drugs which inhibit Src's kinase activity, or the activity of its downstream effectors, might have profound effects on cancer cell behaviour and be useful therapeutic agents...
  6. ncbi Integrin-regulated FAK-Src signaling in normal and cancer cells
    Satyajit K Mitra
    The Scripps Research Institute, Department of Immunology, IMM21 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 18:516-23. 2006
    ....
  7. pmc HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction
    Ronald P Trible
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:27029-38. 2006
    ..These data show that Nef selectively activates Hck, Lyn, and c-Src among SFKs, identifying these kinases as proximal effectors of Nef signaling and potential targets for anti-HIV drug discovery...
  8. ncbi Ras signalling on the endoplasmic reticulum and the Golgi
    Vi K Chiu
    Department of Medicine, Cell Biology and Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Nat Cell Biol 4:343-50. 2002
    ..Thus, Ras signalling is not limited to the PM, but also proceeds on the endomembrane...
  9. ncbi Structure and regulation of Src family kinases
    Titus J Boggon
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Oncogene 23:7918-27. 2004
    b>Src family kinases are prototypical modular signaling proteins. Their conserved domain organization includes a myristoylated N-terminal segment followed by SH3, SH2, and tyrosine kinase domains, and a short C-terminal tail...
  10. pmc The Src family tyrosine kinase Fyn regulates natural killer T cell development
    P Gadue
    Graduate Program in Immunology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Exp Med 190:1189-96. 1999
    ..The fyn mutation defines the first signaling molecule that is selectively required for NK T cell, but not for T lymphocyte or NK cell development...
  11. ncbi Src family kinases: regulation of their activities, levels and identification of new pathways
    Evan Ingley
    Cell Signalling Group, Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, WA, Australia
    Biochim Biophys Acta 1784:56-65. 2008
    ..Thus, a single phosphotyrosine residue within Cbp co-ordinates a two-phase process involving distinct negative regulatory pathways that allow inactivation, followed by degradation, of SFKs...
  12. ncbi Targeting SRC family kinases inhibits growth and lymph node metastases of prostate cancer in an orthotopic nude mouse model
    Serk In Park
    The Program in Cancer Biology, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, TX 77030, USA
    Cancer Res 68:3323-33. 2008
    ..Therefore, we conclude that SFKs are promising therapeutic targets for treatment of human prostate cancer and that Src and Lyn activities affect different cellular functions required for prostate tumor growth and progression...
  13. ncbi Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases
    M Kawabuchi
    Division of Protein Metabolism, Institute for Protein Research, Osaka University, Suita, Japan
    Nature 404:999-1003. 2000
    ..These findings reveal Cbp as a new component of the regulatory mechanism controlling the activity of membrane-associated Src-PTKs...
  14. ncbi Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis
    Roland Reinehr
    Clinic for Gastroenterology, Heinrich Heine University Dusseldorf, D 40225 Dusseldorf, Germany
    J Biol Chem 280:27179-94. 2005
    ..The data suggest that CD95L-induced apoptosis involves a sphingomyelinase- and PKCzeta-dependent activation of NADPH oxidase isoforms, which is required for Yes/EGFR/CD95 interactions as upstream events of CD95 activation...
  15. pmc EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion
    A Mariotti
    Cellular Biochemistry and Biophysics Program, Department of Surgery, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Cell Biol 155:447-58. 2001
    ..These results suggest that disruption of hemidesmosomes mediated by Fyn is a prerequisite for normal keratinocyte migration and squamous carcinoma invasion...
  16. ncbi Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and modulate Bcr-Abl transforming activity
    Malcolm A Meyn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Biol Chem 281:30907-16. 2006
    ..arrest and apoptosis in Bcr-Abl-transformed cells, suggesting that cell transformation by Bcr-Abl involves Src family kinases (Wilson, M. B., Schreiner, S. J., Choi, H. J., Kamens, J., and Smithgall, T. E...
  17. ncbi Src protein-tyrosine kinase structure and regulation
    Robert Roskoski
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1100 Florida Avenue, New Orleans, LA 70119, USA
    Biochem Biophys Res Commun 324:1155-64. 2004
    ..Amino acid residues in the alphaD helix near the catalytic loop in the large lobe of C-terminal Src kinase serve as a docking site for the physiological substrate (Src) but not for an artificial substrate (polyGlu(4)Tyr)...
  18. ncbi Src kinase regulation by phosphorylation and dephosphorylation
    Robert Roskoski
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1100 Florida Avenue, New Orleans, LA 70119, USA
    Biochem Biophys Res Commun 331:1-14. 2005
    ....
  19. ncbi Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation
    Valentino Parravicini
    Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892 1820, USA
    Nat Immunol 3:741-8. 2002
    ..Fyn-deficiency impaired degranulation, whereas Lyn-mediated signaling and calcium was normal. Thus, Fc epsilon RI-dependent mast cell degranulation involves cross-talk between Fyn and Lyn kinases...
  20. ncbi FAK regulates biological processes important for the pathogenesis of cancer
    Veronica Gabarra-Niecko
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Cancer Metastasis Rev 22:359-74. 2003
    ..In addition, the emerging theme of interactions between the FAK and growth factor signaling pathways will be described. The evidence presented in this review provides a compelling case for a role for FAK in the pathology of human cancer...
  21. ncbi Structure and dynamic regulation of Src-family kinases
    J R Engen
    Department of Chemistry and Chemical Biology and the Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, Massachusetts, 02115, USA
    Cell Mol Life Sci 65:3058-73. 2008
    ..This review focuses on biological, biophysical, and computational studies that reveal conformationally distinct active states within this unique kinase family...
  22. ncbi Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product
    M Sudol
    Laboratory of Molecular Oncology, Rockefeller University, New York, NY 10021
    Oncogene 9:2145-52. 1994
    ..Further characterization of YAP65 should illuminate Yes signaling pathways and could also identify a novel link between protein-tyrosine and serine kinases...
  23. ncbi Not so strange bedfellows: G-protein-coupled receptors and Src family kinases
    Deirdre K Luttrell
    Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
    Oncogene 23:7969-78. 2004
    ..Several mechanisms, from the direct association of Src family kinases with GPCRs or receptor-associated proteins, to the transactivation of receptor tyrosine kinases and focal ..
  24. pmc A phosphotyrosine displacement mechanism for activation of Src by PTPalpha
    X M Zheng
    Department of Molecular Biology, Cornell University, Ithaca, NY 14853, USA
    EMBO J 19:964-78. 2000
    ..The displacement mechanism provides another potential control point for physiological regulation of Src-family signal transduction pathways...
  25. pmc Mutual regulation of Src family kinases and the neurotrophin receptor TrkB
    Yang Z Huang
    Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 285:8207-17. 2010
    ..We investigated the interplay of Src family kinases (SFKs) and TrkB to better understand mechanisms of TrkB signaling in physiological and pathological ..
  26. ncbi Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/"triple-negative" breast cancer cell lines growing in vitro
    Richard S Finn
    Department of Medicine, Division of Hematology, Oncology Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 11 934 Factor Bldg, Los Angeles, CA 90095, USA
    Breast Cancer Res Treat 105:319-26. 2007
    ..e. hormonal manipulation or trastuzumab)...
  27. ncbi The protein phosphatase activity of PTEN regulates SRC family kinases and controls glioma migration
    Nandini Dey
    Division of Pediatric Hematology Oncology, Aflac Cancer Center and Blood Disorders Service, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cancer Res 68:1862-71. 2008
    ..we show that the stable overexpression of COOH-terminal Src kinase, the physiologic negative regulator of SRC family kinases (SFK), or treatment with the SFK inhibitor PP1 abrogates glioma migration...
  28. pmc Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk/Bmx, Src, and focal adhesion kinase
    L F Lee
    Department of Biological Chemistry and Cancer Center, University of California at Davis, 4645 2nd Ave, Sacramento, CA 95817, USA
    Mol Cell Biol 21:8385-97. 2001
    ..ii) Tyrosine kinases are involved in neurotrophic factor-mediated AR activation and, as such, may serve as targets of future therapeutics, to be used in conjunction with current antihormone and antineuropeptide therapies...
  29. ncbi Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts
    J Su
    Department of Pharmacology, Kaplan Cancer Center, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Curr Biol 9:505-11. 1999
    ..Whereas the identity of such inhibitory Tyr527 kinases has been well established, no corresponding phosphatases have been identified that, under physiological conditions, function as positive regulators of c-Src and Fyn in fibroblasts...
  30. ncbi A critical role for Lyn in acute myeloid leukemia
    Cédric Dos Santos
    INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Département d Oncogenèse, Signalisation et Innovation thérapeutique, Universite Toulouse III Paul Sabatier, IFR30, Toulouse, France
    Blood 111:2269-79. 2008
    ..The Src family kinases (SFKs) appeared constitutively activated in most cases, including in the CD34(+)CD38(-)CD123(+) compartment ..
  31. pmc Src family kinases mediate neutrophil adhesion to adherent platelets
    Virgilio Evangelista
    Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, Via Nazionale 8 A, 66030 Santa Maria Imbaro, Italy
    Blood 109:2461-9. 2007
    ..These results definitely establish a role for SFKs in PMN recruitment by activated platelets and suggest novel targets to disrupt the pathophysiologic consequences of platelet-leukocyte interactions in vascular disease...
  32. ncbi Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior
    Valerie G Brunton
    Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow, United Kingdom
    Cancer Res 65:1335-42. 2005
    ..These studies have implications for tumor progression with respect to the use of Src kinase inhibitors...
  33. ncbi Insights into Src kinase functions: structural comparisons
    J C Williams
    Howard Hughes Medical Institute, Dept of Biochemistry and Molecular Biophysics, Columbia University, New York 10032, USA
    Trends Biochem Sci 23:179-84. 1998
    ..This motion could provide insights into the various mechanisms used to regulate kinase activity...
  34. ncbi Cholesterol-rich membrane rafts and Lyn are involved in phagocytosis during Pseudomonas aeruginosa infection
    Shibichakravarthy Kannan
    Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA
    J Immunol 180:2396-408. 2008
    ..Our investigations demonstrate that Lyn along with membrane rafts plays a fundamental role in phagocytosis by alveolar macrophages during infection...
  35. ncbi Regulation of ultraviolet B-induced phosphorylation of histone H3 at serine 10 by Fyn kinase
    Zhiwei He
    Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA
    J Biol Chem 280:2446-54. 2005
    ..These results indicate that Fyn kinase plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10...
  36. ncbi Cellular functions regulated by Src family kinases
    S M Thomas
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Cell Dev Biol 13:513-609. 1997
    ..This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that ..
  37. pmc LYN is a mediator of epithelial-mesenchymal transition and a target of dasatinib in breast cancer
    Yoon La Choi
    Department of Pathology and Division of Breast and Endocrine Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    Cancer Res 70:2296-306. 2010
    ....
  38. ncbi Activation of stat3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression
    Nills Diaz
    Pathology, H Lee Moffitt Cancer Center and Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, Florida, USA
    Clin Cancer Res 12:20-8. 2006
    ....
  39. pmc Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis
    M P Kim
    Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Box no 173, Houston, TX 77030 4009, USA
    Cell Tissue Res 335:249-59. 2009
    b>Src family kinases (SFKs) are signaling enzymes that have long been recognized to regulate critical cellular processes such as proliferation, survival, migration, and metastasis...
  40. pmc Force sensing by mechanical extension of the Src family kinase substrate p130Cas
    Yasuhiro Sawada
    Department of Biological Sciences, Columbia University, Sherman Fairchild Center Room 715, MC 2416, 1212 Amsterdam Avenue, New York, NY 10027, USA
    Cell 127:1015-26. 2006
    ..Cas substrate domain protein (CasSD) in vitro and found a remarkable enhancement of phosphorylation by Src family kinases with no apparent change in kinase activity...
  41. pmc Sustained activation of Lyn tyrosine kinase in vivo leads to autoimmunity
    Margaret L Hibbs
    Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria 3050, Australia
    J Exp Med 196:1593-604. 2002
    ..These studies highlight the difficulty in maintaining tolerance in the face of chronic stimulation and emphasize the pivotal role of Lyn in B cell signaling...
  42. ncbi Src continues aging: current and future clinical directions
    Scott Kopetz
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030 4009, USA
    Clin Cancer Res 13:7232-6. 2007
    ..Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor ..
  43. pmc Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase
    Sandra Odom
    Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 199:1491-502. 2004
    ..Thus, lyn-/- mice and mast cells thereof show multiple allergy-associated traits, causing reconsideration of the possible efficacy in therapeutic targeting of Lyn in allergic disease...
  44. ncbi Inhibition of Src family kinases blocks epidermal growth factor (EGF)-induced activation of Akt, phosphorylation of c-Cbl, and ubiquitination of the EGF receptor
    C Kenneth Kassenbrock
    Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA
    J Biol Chem 277:24967-75. 2002
    ..PP1 treatment blocks EGF-induced activation of the anti-apoptotic protein kinase Akt suggesting that Src may regulate activation of Akt, perhaps by a Src --> c-Cbl --> phosphatidylinositol 3'-kinase --> Akt pathway...
  45. ncbi Kinases of the Src family: structure and functions
    A G Tatosyan
    Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia
    Biochemistry (Mosc) 65:49-58. 2000
    ....
  46. pmc Focal adhesions require catalytic activity of Src family kinases to mediate integrin-matrix adhesion
    Leiming Li
    The Ben May Institute for Cancer Research and Center for Molecular Oncology, Committee on Cell Physiology, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell Biol 22:1203-17. 2002
    ..rather than caspase-mediated apoptosis that may result from possible loss of survival signals mediated by Src family kinases. We suggest that endogenous Src family kinases are essential for FAs through activation of Rap1 in ..
  47. pmc SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines
    Jie Zhang
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Am J Pathol 170:366-76. 2007
    ..We conclude that SFKs are activated in NSCLC biopsy samples, promote the survival of EGFR-dependent NSCLC cells, and should be investigated as therapeutic targets in NSCLC patients...
  48. ncbi JAKs, STATs and Src kinases in hematopoiesis
    Sushil G Rane
    Laboratory of Cell Regulation and Carcinogenesis, NCI, NIH, Bldg 41, C629, 41 Library Drive, Bethesda, Maryland, MD 20892, USA
    Oncogene 21:3334-58. 2002
    ....
  49. pmc Intracellular reactive oxygen species activate Src tyrosine kinase during cell adhesion and anchorage-dependent cell growth
    Elisa Giannoni
    Dipartimento di Scienze Biochimiche, Viale Morgagni 50, 50134 Firenze, Italy
    Mol Cell Biol 25:6391-403. 2005
    ..Therefore we propose that, in addition to the known phosphorylation/dephosphorylation circuitry, redox regulation of Src activity is required during both cell attachment to the extracellular matrix and tumorigenesis...
  50. ncbi The interplay between Src family kinases and receptor tyrosine kinases
    Paul A Bromann
    Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA
    Oncogene 23:7957-68. 2004
    ....
  51. ncbi Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts
    Sebastien Tauzin
    Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    Blood 111:2310-20. 2008
    ..The Lyn-Cbp/PAG signalosome appears to control proliferation and survival in most B-NHLs and constitutes a therapeutic target in B-NHL cells that exhibit oncogenic "addiction" to the Lyn kinase...
  52. ncbi The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells
    Darren F Seals
    Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    Cancer Cell 7:155-65. 2005
    ..Thus, Tks5/Fish appears to be required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells...
  53. ncbi An allelic series at the PDGFalphaR locus indicates unequal contributions of distinct signaling pathways during development
    Richard A Klinghoffer
    Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Dev Cell 2:103-13. 2002
    ..receptor (PDGFalphaR) that selectively eliminate its capacity to activate PI3 kinase (alpha(PI3K)) or Src family kinases (alpha(Src))...
  54. ncbi Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice
    S G Grant
    Center for Neurobiology and Behavior, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032
    Science 258:1903-10. 1992
    ..Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus...
  55. ncbi Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab
    Yang Lu
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Res 67:8240-7. 2007
    ....
  56. ncbi Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases
    C Hugh Reynolds
    The MRC Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, London, UK
    J Biol Chem 283:18177-86. 2008
    ....
  57. pmc Transforming potential of Src family kinases is limited by the cholesterol-enriched membrane microdomain
    Chitose Oneyama
    Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Mol Cell Biol 29:6462-72. 2009
    The upregulation of Src family kinases (SFKs) has been implicated in cancer progression, but the molecular mechanisms regulating their transforming potentials remain unclear...
  58. ncbi Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity
    D H Boschelli
    Chemical Sciences, Wyeth Ayerst Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    J Med Chem 44:3965-77. 2001
    ..IC(50) of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in ..
  59. ncbi Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development
    Kaoru Saijo
    Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021, USA
    Nat Immunol 4:274-9. 2003
    ..Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development...
  60. ncbi Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells
    Valerie Hernandez-Hansen
    Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, CRF 205, 2325 Camino de Salud, Albuquerque, NM 87131, USA
    J Immunol 173:100-12. 2004
    ..The unexpected absence of the transient receptor potential channel, Trpc4, from Lyn(-/-) BMMCs may additionally contribute to their altered signaling properties...
  61. pmc RACK1 regulates G1/S progression by suppressing Src kinase activity
    Vidya Mamidipudi
    Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305 5187, USA
    Mol Cell Biol 24:6788-98. 2004
    ..We also show that Stat3 is required for Rac1 induction of Myc. Our results reveal a novel mechanism of cell cycle control in late G(1) that works via an endogenous inhibitor of the Src kinase...
  62. pmc Determination of hierarchical relationship of Src and Rac at subcellular locations with FRET biosensors
    Mingxing Ouyang
    Department of Bioengineering, Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana Champaign, IL 61801, USA
    Proc Natl Acad Sci U S A 105:14353-8. 2008
    ..In summary, ECFP/YPet may serve as a general FRET pair for the development of highly sensitive biosensors to allow the determination of molecular hierarchies at subcellular locations in live cells...
  63. pmc Observing FcepsilonRI signaling from the inside of the mast cell membrane
    B S Wilson
    Department of Pathology and Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA
    J Cell Biol 149:1131-42. 2000
    ..The sequential association of FcstraightepsilonRI with Lyn, Syk, and coated pits in topographically distinct membrane domains implicates membrane segregation in the regulation of FcstraightepsilonRI signaling...
  64. ncbi An integrated genomic-based approach to individualized treatment of patients with advanced-stage ovarian cancer
    Holly K Dressman
    Division of Gynecologic Surgical Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
    J Clin Oncol 25:517-25. 2007
    ..We have used gene expression profiles to identify patients likely to be resistant to primary platinum-based chemotherapy and also to identify alternate targeted therapeutic options for patients with de novo platinum-resistant disease...
  65. ncbi Src family protein tyrosine kinases: cooperating with growth factor and adhesion signaling pathways
    J T Parsons
    Department of Microbiology, Health Sciences Center, University of Virginia, Charlottesville, VA 22908, USA
    Curr Opin Cell Biol 9:187-92. 1997
    ..Recent developments show that Src family kinases may cooperate with the epidermal growth factor and platelet-derived growth factor receptors and the integrin-..
  66. pmc Is expression or activation of Src kinase associated with cancer-specific survival in ER-, PR- and HER2-negative breast cancer patients?
    Beatrix Elsberger
    Section of Surgery, Division of Cancer Sciences and Molecular Pathology, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
    Am J Pathol 175:1389-97. 2009
    ..It is therefore essential to appropriately identify with the correct biomarkers which patients are most likely to respond to Src inhibitors...
  67. pmc Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice
    P L Schwartzberg
    National Cancer Institute, University of Texas Health Science Center, San Antonio, Texas 78284, USA
    Genes Dev 11:2835-44. 1997
    ..These results suggest that there are essential kinase-independent functions for Src in vivo. Biochemical examination of osteoclasts from these mice suggest that Src may function in part by recruiting or activating other tyrosine kinases...
  68. ncbi Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state
    Matthew D Potter
    Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA
    J Biol Chem 280:31906-12. 2005
    ..These findings demonstrate that a single phosphorylation event within the VE-cadherin cytoplasmic tail is sufficient to maintain cells in a mesenchymal state...
  69. ncbi SRC family kinase activity is up-regulated in hormone-refractory prostate cancer
    Oleg Tatarov
    Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, Glasgow Royal Infirmary, Glasgow, UK
    Clin Cancer Res 15:3540-9. 2009
    ..This study was designed to determine if SFK activation was up-regulated with the development of AIPC and if patients could be selected who were more likely to respond to therapy...
  70. ncbi ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing
    Yutaka Matsubayashi
    Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Curr Biol 14:731-5. 2004
    ..Thus, our results identify specific requirements of ERK1/2 MAP kinase for epithelial cell sheet movement...
  71. ncbi FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly
    Donna J Webb
    Department of Cell Biology, UVA School of Medicine, P O Box 800732, Charlottesville, Virginia 22908 0732, USA
    Nat Cell Biol 6:154-61. 2004
    ....
  72. pmc Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice
    Yiguo Hu
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Proc Natl Acad Sci U S A 103:16870-5. 2006
    ..However, curing B-ALL and CML mice requires killing leukemic stem cells insensitive to both imatinib and dasatinib. Besides BCR-ABL and SRC kinases, stem cell pathways must be targeted for curative therapy of Ph(+) leukemia...
  73. pmc A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages
    M T Crowley
    G W Hooper Foundation, University of California, San Francisco, California 94143 0552, USA
    J Exp Med 186:1027-39. 1997
    ..Additionally, our findings provide evidence to support a model of sequential tyrosine kinase activation by FcgammaR's analogous to models of signaling by the B and T cell antigen receptors...
  74. pmc Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription
    Sayyed K Zaidi
    Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655 0106, USA
    EMBO J 23:790-9. 2004
    ..Our results suggest that Src/Yes signals are integrated through organization of Runx2-YAP transcriptional complexes at subnuclear sites to attenuate skeletal gene expression...
  75. pmc Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation
    M Kovarova
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic
    Mol Cell Biol 21:8318-28. 2001
    ....
  76. ncbi A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation
    I Dikic
    Department of Pharmacology, New York University Medical Center, 10016, USA
    Nature 383:547-50. 1996
    ..Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk...
  77. pmc Src-mediated coupling of focal adhesion kinase to integrin alpha(v)beta5 in vascular endothelial growth factor signaling
    Brian P Eliceiri
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Cell Biol 157:149-60. 2002
    ..Our findings indicate that Src can coordinate specific growth factor and extracellular matrix inputs by recruiting integrin alpha(v)beta5 into a FAK-containing signaling complex during growth factor-mediated biological responses...
  78. ncbi Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation
    Weidong Wu
    Center for Environmental Medicine and Lung Biology, The Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:24252-7. 2002
    ..These data demonstrate that Src-dependent phosphorylation of the EGFR at Tyr-845 is required for EGFR transactivation and Zn2+-induced Ras activation...
  79. ncbi SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models
    Jennifer M Golas
    Department of Oncology, Wyeth Research, Pearl River, New York 10965, USA
    Cancer Res 65:5358-64. 2005
    ..These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer...
  80. ncbi Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells
    Shibichakravarthy Kannan
    Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 558203, USA
    Eur J Immunol 36:1739-52. 2006
    ..This report brings out a new role of Lyn in infectious diseases and indicates potential new targets for prevention and treatment of infections...
  81. ncbi Tyrosine kinase and cooperative TGFbeta signaling in the reproductive organs of Schistosoma mansoni
    Jürgen Knobloch
    Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, D 40225 Dusseldorf, Germany
    Exp Parasitol 117:318-36. 2007
    ..Finally, we take advantage from the schistosome genome project to propose a model for the regulation of vitelline-cell production and differentiation...
  82. ncbi New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance
    Hagop M Kantarjian
    Department of Leukemia, MD Anderson Cancer Center, Houston, Texas 77030, USA
    Ann Intern Med 145:913-23. 2006
    ..newer tyrosine kinase inhibitors, including dasatinib (a multitargeted kinase inhibitor of BCR-ABL and Src family kinases) and nilotinib (AMN107, a selective BCR-ABL inhibitor), may provide promising treatment options for patients ..
  83. ncbi Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway
    H Chin
    First Department of Internal Medicine and School of Allied Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Blood 91:3734-45. 1998
    ..In addition, Lyn was demonstrated to phosphorylate the EpoR and Stat5 on tyrosines in vitro. These results suggest that Lyn may play a role in activation of the Jak2/Stat5 and other signaling pathways by the EpoR...
  84. ncbi Activated SRC protein tyrosine kinase is overexpressed in late-stage human ovarian cancers
    Jon R Wiener
    Department of Molecular Therapeutics, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Gynecol Oncol 88:73-9. 2003
    ..The objective of this study was to determine if the Src tyrosine kinase is overexpressed and activated in late-stage human ovarian cancers...
  85. ncbi Src family kinases, key regulators of signal transduction
    Sarah J Parsons
    Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, VA 22908 0734, USA
    Oncogene 23:7906-9. 2004
    ..In this volume, we have attempted to provide the reader with an overview of the current understanding of the function of Src family kinases in the regulation of selected cellular signaling pathways.
  86. pmc Cholesterol and lipid microdomains stabilize the postsynapse at the neuromuscular junction
    Raffaella Willmann
    Department of Neurochemistry, Brain Research Institute, University of Zurich, Zurich, Switzerland
    EMBO J 25:4050-60. 2006
    ....
  87. ncbi Role of Raf in vascular protection from distinct apoptotic stimuli
    Alireza Alavi
    Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 301:94-6. 2003
    ..These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis...
  88. ncbi Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src
    H He
    Vascular Biology Center, The Medical College of Georgia, Augusta, Georgia 30912 2500, USA
    J Biol Chem 274:25130-5. 1999
    ..These results suggest that NO and PGI(2) function in parallel in mediating the effects of VEGF...
  89. pmc Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors
    Emma Sandilands
    Cancer Research UK Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
    EMBO Rep 8:1162-9. 2007
    ..Chemical and genetic inhibition studies showed strikingly different requirements for Src family kinases in FGFR1-mediated signalling; activation of the phosphoinositide-3 kinase-Akt pathway is severely attenuated,..
  90. ncbi Epidermal growth factor receptor exposed to oxidative stress undergoes Src- and caveolin-1-dependent perinuclear trafficking
    Elaine M Khan
    Signal Transduction Laboratory, Department of Internal Medicine, University of California, School of Medicine, Davis, California 95616, USA
    J Biol Chem 281:14486-93. 2006
    ..Thus, oxidative stress may have a role in tumorigenesis by not only activating the EGFR but also by promoting prolonged activation of the receptor both at the plasma membrane and within the cell...
  91. pmc Binding of Src to Na+/K+-ATPase forms a functional signaling complex
    Jiang Tian
    Department of Pharmacology, Medical University of Ohio, Toledo, OH 43614, USA
    Mol Biol Cell 17:317-26. 2006
    ..These new findings illustrate a novel molecular mechanism of signal transduction involving the interaction of a P-type ATPase and a nonreceptor tyrosine kinase...
  92. ncbi Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease
    M L Hibbs
    Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia
    Cell 83:301-11. 1995
    ..Collectively, these results implicate LYN as having an indispensable role in immunoglobulin-mediated signaling, particularly in establishing B cell tolerance...
  93. ncbi Src kinases: a hub for NMDA receptor regulation
    Michael W Salter
    Programme in Brain and Behaviour, The Hospital for Sick Children, University of Toronto, Ontario, Canada
    Nat Rev Neurosci 5:317-28. 2004
  94. pmc SRC family kinases and receptors: analysis of three activation mechanisms by dynamic systems modeling
    Hendrik Fuss
    School of Biomedical Sciences, University of Ulster, Coleraine, Ireland
    Biophys J 94:1995-2006. 2008
    b>Src family kinases (SFKs) interact with a number of cellular receptors. They participate in diverse signaling pathways and cellular functions...
  95. pmc Growth factors outside of the platelet-derived growth factor (PDGF) family employ reactive oxygen species/Src family kinases to activate PDGF receptor alpha and thereby promote proliferation and survival of cells
    Hetian Lei
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 284:6329-36. 2009
    ..Indeed, preventing expression or blocking the kinase activity of Src family kinases suppressed non-PDGF-dependent tyrosine phosphorylation of PDGFRalpha...
  96. ncbi Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion
    Severine Van Slambrouck
    Laboratory of Biochemical and Biomedical Research, Department of Chemistry, New Mexico Tech, Socorro, NM, USA
    Int J Oncol 31:1501-8. 2007
    ..These findings support the notion that the alpha1-integrin- and src-dependent signalosome is a relevant therapeutic target against tumor progression in colon cancer patients...
  97. ncbi Ouabain induces endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells by a clathrin-dependent mechanism
    Jiang Liu
    The Department of Medicine, Medical College of Ohio, Toledo, Ohio, USA
    Kidney Int 66:227-41. 2004
    ..We have demonstrated that ouabain causes dose- and time-dependent decreases in (86)Rb uptake in porcine proximal tubular (LLC-PK1) cells. The present study addresses the molecular mechanisms involved in this process...
  98. pmc A src family tyrosine kinase inhibits neurotransmitter release from neuronal cells
    H Ohnishi
    Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan
    Proc Natl Acad Sci U S A 98:10930-5. 2001
    ..It is possible that a src family tyrosine kinase, through the regulation of actin dynamics, has an inhibitory function to regulate neurotransmitter release...
  99. pmc G-protein-gated inwardly rectifying potassium channels regulate ADP-induced cPLA2 activity in platelets through Src family kinases
    Haripriya Shankar
    Department of Physiology, Sol Sherry Thrombosis Research Center, Temple University, Rm 224OMS, 3420 N Broad St, Philadelphia, PA 19140, USA
    Blood 108:3027-34. 2006
    ....
  100. pmc Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases
    Leiming Li
    Committee on Cell Physiology and The Ben May Institute for Cancer Research and Center for Molecular Oncology, The University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell Biol 23:2883-92. 2003
    ..These results therefore provide formal evidence that CrkL plays a specific role in integrin-induced migration as a downstream mediator of Src...
  101. ncbi Src and Pyk2 mediate G-protein-coupled receptor activation of epidermal growth factor receptor (EGFR) but are not required for coupling to the mitogen-activated protein (MAP) kinase signaling cascade
    J Andreev
    Department of Pharmacology, New York University School of Medicine, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA
    J Biol Chem 276:20130-5. 2001
    ..In addition, EGFR, Src family kinases, and Pyk2 are not required for linking GPCRs with the MAP kinase signaling cascade.

Research Grants65

  1. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford A Lowell; Fiscal Year: 2013
    ..This will lead to better design of therapeutcs to target immune diseases, as well as leukemia and lymphoma. ..
  2. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
    ..We will perform in vitro studies to delineate the effect of c-Cbl mutations on tyrosine kinase receptors and Src family kinases and explain whether pathologic mechanisms are mediated by mutant c-Cbl...
  3. Regulation of Signaling Receptor Activity by LRP-1
    Steven L Gonias; Fiscal Year: 2013
    ..activate cell-signaling pathways leading to factors such as ERK/MAP kinase, Akt and possibly Src family kinases and NF-kB...
  4. Innate and Adaptive Immune Mechanisms in Arthritis
    RICHARD J BUCALA; Fiscal Year: 2013
    ..Such inhibitors may show greatest efficacy in those patients with high-expression MIF alleles and who manifest an MIF-dependent form of inflammatory disease. ..
  5. Mechanisms of pox virus motility and release
    Daniel Kalman; Fiscal Year: 2012
    ..g., FDA-approved Gleevec) limit poxvirus egress and release both in vitro and in vivo, a critical prelude for the potential therapeutic use of Gleevec and related compounds as therapeutics for poxviral infections. ..
  6. INTEGRIN SIGNALING IN HEMOSTASIS AND BLOOD DISEASES
    Sanford J Shattil; Fiscal Year: 2012
    ..that outside-in signaling in platelets is triggered by dynamic and direct interactions between integrins, Src family kinases and Src regulatory proteins...
  7. Novel Strategy for Lung Cancer Treatment Using IGF-1R Inhibitor
    Ho Young Lee; Fiscal Year: 2013
    ..abstract_text> ..
  8. Cadherin-catenin Mediated Contact Inhibition of Cell Growth
    Barry M Gumbiner; Fiscal Year: 2013
    ..major pathways;inhibition of growth factor receptor signaling, which we now find results from inhibition of Src family kinases (SFKs);and our preliminary findings also implicate the Hippo signaling pathway, in particular the nuclear ..
  9. Tau in cancer cells
    Gloria Lee; Fiscal Year: 2010
    ..The data from this application will further our understanding of how abnormal tau might lead to cell death. ..
  10. Regulation of the hematopoietic-cell transmembrane phosphatases CD45 and CD148
    Tanya S Freedman; Fiscal Year: 2010
    ..Understanding the regulation of these signaling proteins will help us better understand the balance of signals necessary for maintaining appropriate growth patterns and sensitivity in immune cells ..
  11. Targeting Entry Pathways in Leishmaniasis
    DAWN MARIE WETZEL; Fiscal Year: 2013
    ..between [unreadable]2 integrin and Abl allow promastigote uptake by macrophages, 2) interactions among FcR, Src family kinases, and Arg allow amastigote uptake by macrophages, and 3) drugs that can inhibit these signaling proteins will ..
  12. Validation of Src kinases as Anti-Dengue Viral Targets
    PRISCILLA LI NING YANG; Fiscal Year: 2012
    ..From an initial series of screens, we found that inhibitors of Src family kinases (SFK) are potent inhibitors of DENV in vitro...
  13. Src Family Kinases and Control of Epithelial Cell Paracellular Permeability
    KURT F AMSLER; Fiscal Year: 2012
    ....
  14. Src Family Kinases - Mediated Ischemic Neonatal Brain Injury
    Xiangning Jiang; Fiscal Year: 2010
    ..mediated by NMDA-type glutamate receptors (NMDAR) is a major trigger of HI brain injury, and members of the Src family kinases (SFKs, mainly Fyn and Src) act as a molecular hub for the control of NMDAR...
  15. Eosinophils and lung immunity to Pneumocystis
    Chad Steele; Fiscal Year: 2013
    ....
  16. Neutrophil Chemotaxis in Autoinflammation
    Anna Huttenlocher; Fiscal Year: 2013
    ..this research is that neutrophil chemotaxis, mediated by the balance between reactive oxygen species (ROS), Src family kinases and tyrosine phosphatase signaling modulates the development and resolution of inflammation in vivo...
  17. Ponce School of Medicine - Moffitt Cancer Center Partnership
    WARREN JACKSON PLEDGER; Fiscal Year: 2011
    ..Appleyard in the Minority-Serving Institute (MSI) to successfully compete for a R01 grant from the National Cancer Institute (NCI) and will increase the quality of graduate education at the MSI. ..
  18. Beagle: A Supercomputer for Computational Biology, Simulation, and Data Analysis
    Ian Foster; Fiscal Year: 2010
    ..substantial support from the University of Chicago for operations and application support, and an extremely experienced technical staff allows us to propose a system with capabilities unprecedented in academic biomedicine. ..
  19. Functional G Protein pathways in platelet activation
    Satya P Kunapuli; Fiscal Year: 2010
    ..We also hypothesize that HAX-1, HS-1, and Src family kinases are activated downstream of G12/13 pathways, which play an important role in platelet activation...
  20. Neph1 Signaling
    Deepak Nihalani; Fiscal Year: 2010
    ..The Holzman lab demonstrated that Nephrin is phosphorylated on tyrosine residues by Src family kinases (SFK's) suggesting that the Nephrin associated complex is involved in signal transduction...
  21. Fyn Inhibition by AZD0530 for Alzheimers Disease
    Christopher H van Dyck; Fiscal Year: 2013
    ..AZD0530 is a selective inhibitor of Src family kinases, and has been developed primarily for the treatment of cancer...
  22. The Coordination of Netrin Signal Transduction
    Guofa Liu; Fiscal Year: 2011
    ..the coordination of protein phosphorylation in netrin/DSCAM and netrin/DCC signaling, relationship of Src family kinases and JNK1 in netrin signal transduction cascades and the functional coordination of DSCAM and DCC in netrin-..
  23. The role of Fyn and Srcasm in UVB-induced cutaneous neoplasia
    John T Seykora; Fiscal Year: 2013
    ..This work will also provide new candidate molecules that may improve topical therapies to treat AKs and cSCCs in patients. ..
  24. Non-Toll-like receptor innate immune signaling
    David M Underhill; Fiscal Year: 2012
    ..In Aim 1 will define the mechanisms by which Dectin-1 and yeast activate Src family kinases and Syk in macrophages, dendritic cells, and neutrophils...
  25. HUMAN BLOOD MONOCYTE RECEPTOR EXPRESSION AND MODULATION
    Alan D Schreiber; Fiscal Year: 2010
    ..Also, while phosphorylation of tyrosines in the ITAM by Src family kinases (SRTKs) is an essen- tial step for initiation of phagocytosis, our evidence indicates that endocytosis is ..
  26. Therapeutic targeting of Src kinase signal transduction pathways in AML
    Martin Carroll; Fiscal Year: 2013
    ..of both lyn and lck tyrosine kinases in AML cells suggesting that Lyn and Lck, two members of the Src family kinases (SFKs) may contribute to activation of signaling pathways in AML...
  27. Dissecting the Role of Src Family Kinases in Breast Cancer Brain Metastasis
    Siyuan Zhang; Fiscal Year: 2013
    Project Summary/Abstract Title: Dissecting the Role of Src Family Kinases in Breast Cancer Brain Metastasis PI: Siyuan Zhang, M.D., Ph.D., The University of Texas M.D. Anderson Cancer Center I received my M.D...
  28. Complexes of HIV-1 Nef with Src-family Kinases as Therapeutic Targets
    Lori A Emert Sedlak; Fiscal Year: 2010
    ..This compound represents the first to target a viral protein:host cell protein kinase complex, providing a new lead for anti-HIV drug development. ..
  29. Regulation of RUNX1 Multiprotein Complex Formation during Hematopoiesis
    Alan B Cantor; Fiscal Year: 2013
    ..This work has the potential for immediate impact, as small molecule inhibitors of signaling pathways we hypothesize to impact RUNX1 activity are already clinically available and/or in testing. ..
  30. INTESTINAL CELL GROWTH CONTROL: ROLE OF TYROSINE KINASES
    CHRISTINE ANN CARTWRIGHT; Fiscal Year: 2013
    ..Exploitation of these multiple functions could be used to develop new and more powerful and selective strategies for treatment of human colon cancer. ..
  31. ADAM17-NRG-1 Signaling in Acute Lung Injury
    James H Finigan; Fiscal Year: 2013
    ..1.2: Define the role of Src family kinases in ADAM17 tyrosine phosphorylation and NRG-1 shedding...
  32. Cytoskeleton - Membrane Interactions
    ELIZABETH LUNA; Fiscal Year: 2009
    ..to the tight association of lipid raft organizing proteins (flotillins, stomatin) and signaling proteins (Src family kinases, heterotrimeric Gi proteins, matrix metalloproteinase) with filamentous actin, myosins I and II, and other ..
  33. THE ROLE OF GLIOTRANSMISSION IN MEDIATING THE CENTRAL EFFECTS OF ALCOHOL
    Sally McIver; Fiscal Year: 2012
    ..transporter 1, and that sensitivity to and consumption of alcohol can be mediated by activation of the src family kinases (SFK) and a known substrate, the NR2B subunit of the NMDAR...
  34. Abl Kinases in growth factor signaling, motility, and invasion
    Rina Plattner; Fiscal Year: 2011
    ..Previously, we showed that Abl kinases are activated downstream of growth factor receptors via Src family kinases and PLC-yl, and influence growth factor-mediated cytoskeletal reorganization and migration in fibroblasts...
  35. SOLUTE TRANSPORT MECHANISMS IN THE CILIARY BODY
    Nicholas A Delamere; Fiscal Year: 2013
    ..The studies proposed here will improve our understanding of regulatory mechanisms for aqueous humor formation and may identify targets to consider in the search for new drugs to reduce aqueous production. ..
  36. Investigation of the catalytic and non-catalytic roles of Src family kinases in o
    Stephen Leonard; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Disregulation of Src family kinases (SFKs) plays an important role in tumor development, specifically metastasis...
  37. Conformational Flexibility in Activation of Scr-Kinase
    Benoit Roux; Fiscal Year: 2013
    ....
  38. Src kinase phosphoregulation of the human mitotic kinesin, Eg5
    Sarah E Rice; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): This proposal is based on a new finding that Src family kinases (SFKs) phosphorylate human Eg5, an essential mitotic kinesin family motor protein...
  39. Regulation of Tumor Cell Differentiation by Src Kinases
    Malcolm A Meyn; Fiscal Year: 2010
    ..We propose to contribute to the understanding of these pathways by testing the hypothesis that oncogenic Src family kinases aberrantly activate signaling pathways that inhibit differentiation of pluripotent cells...
  40. Specialized Program of Research Excellence
    Jennifer Rubin Grandis; Fiscal Year: 2013
    ..Immunity and Immune Escape for EGFR Antibody Therapy;and (4) Therapeutic Mechanisms of Co-Targeting EGFR and Src Family Kinases. The three cores will interact closely to assist the main research projects, developmental research projects ..
  41. Regulation of mediator release from human mast cell by extracellular adenosine.
    GREGORIO VALENZUELA GOMEZ; Fiscal Year: 2012
    ..End of Abstract) ..
  42. Targeting myristoylation of Src family kinases for inhibition of prostate tumorig
    Houjian Cai; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The expression and activity of Src family kinases (SFKs) are highly elevated in numerous human cancers, including prostate cancer...
  43. Structural Biology of HIV Nef-Src Family Kinase Complexes
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2010
    ..Nef interacts with multiple host cell signaling proteins, including the Src family kinases (SFKs) Hck, Lyn, and c-Src...
  44. STAT Mediated TGF-a/EGFR Signaling in squamous cell carcinomas of the head &neck
    Jennifer Rubin Grandis; Fiscal Year: 2012
    ..that EGFR-mediated activation of selected Signal Transducers and Activators of Transcription (STATs) and Src family kinases contribute to SCCHN growth and survival...
  45. Adhesive Signaling by Platelet Integrins
    Sanford J Shattil; Fiscal Year: 2013
    ..activated to promote metastasis, whether specific integrin-interacting proteins such as talin, kindlin and Src family kinases are involved, and whether deletion of a specific tumor suppressor gene, DLC-1, promotes metastasis by ..
  46. Role of mechanically activated Src/mTORC2 signaling on cytoskeletal adaptation
    William Roy Thompson; Fiscal Year: 2013
    ....
  47. Signaling Mechanisms in Leukocyte Transendothelial Migration
    Marcie R Williams; Fiscal Year: 2011
    ..This short cytoplasmic tail associates with activated Src family kinases (SFK), cortactin, and a number of other cytoskeletal adapter proteins...
  48. L1 SIGNALING IN X-LINKED MENTAL RETARDATION
    Patricia Maness; Fiscal Year: 2000
    ..Specific aims are : 1. To characterize the normal interaction of L1 with src family kinases in mouse brain and neuronal cultures. 2...
  49. INTEGRATION OF CYTOKINE RECEPTORS AND IMMUNORECEPTORS SIGNALING PATHWAYS
    Ruslan Medzhitov; Fiscal Year: 2010
    ..depends on a 'priming signal'delivered from a Y-kinase, generally assumed to be the member of a Src family kinases (SFK)...
  50. Structural Biology of HIV-1 Nef with Host Effectors and Small Molecule Inhibitors
    Joanne I Yeh; Fiscal Year: 2013
    ..These studies will provide important mechanistic evidence that the compounds antagonize Nef functions relevant to HIV-1 in a manner predicted by the structural biology. ..
  51. Small Molecule Inhibitors of HIV Nef Signaling
    THOMAS EDWARD SMITHGALL; Fiscal Year: 2013
    ..Successful completion of these studies will provide new tools for understanding Nef interactions with host cell proteins and identify lead compounds for the development of a new class of anti-HIV therapeutics. ..
  52. STRUCTURE AND FUNCTION OF PROTEIN C
    John H Griffin; Fiscal Year: 2013
    ..The findings may well be translatable into future clinical advances. ..
  53. New roles of Src tyrosine kinases in vascular tone
    LIGIA TORO DE STEFANI; Fiscal Year: 2007
    ..The elucidation of primary steps involved in 5-HT and TXA2 smooth muscle stimulation should help in the design of new therapeutic ways to control cardiovascular disease. [unreadable] [unreadable]..
  54. Oligodendrocyte Differentiation and Myelin Biogenesis
    Rashmi Bansal; Fiscal Year: 2007
    ..RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .................................................................................................................................................. 1 Description, ..
  55. SRC-LIKE KINASES IN INTERLEUKIN-3 RECEPTOR SIGNALING
    Steven Anderson; Fiscal Year: 2001
    ..These approaches should also help to identify both substrates phosphorylated, as well as signaling pathways activated, in a Src kinase-dependent manner. ..
  56. SRC KINASES IN THE DEVELOPING NERVOUS SYSTEM
    Patricia Maness; Fiscal Year: 2004
    ..L1 and the 140 kD isoform of NCAM activate MAPK signaling pathways governed by distinct Src family kinases (Src, Fyn) and RhoGTPases (Rac, Rho)...
  57. Caveolins, Caveolae, and Lipid Rafts
    DOUGLAS LUBLIN; Fiscal Year: 2004
    ..of membrane proteins, including GPI-anchored proteins and many lipid-modified signaling proteins such as src family kinases and G proteins...
  58. Arrestin activation probed with mass spectrometry
    Eric Prossnitz; Fiscal Year: 2007
    ..Our results will contribute to our basic knowledge of this key signaling molecule and provide the basis for the design of therapeutic agents related to GPCR signaling. ..
  59. TRANSFUSION BIOLOGY AND MEDICINE
    Pearl Toy; Fiscal Year: 2005
    ..The ultimate goals of this program are to make optimal use of blood products, to evaluate and possibly modify the immune effects and understand and possibly stimulate blood production so as to reduce transfusion needs. ..
  60. Src Family Tyrosine Kinases in Tumor Cell Signaling
    THOMAS SMITHGALL; Fiscal Year: 2007
    ..lacking Src family kinase phosphorylation sites and selective inhibitors will be used to determine whether Src family kinases affect Bcr-Abl activity and sensitivity to STI-571, which selectively inhibits the inactive conformer of Abl...
  61. SRC-FAMILY TYROSINE KINASES IN LYMPHOCYTE SIGNALING
    Paul Stein; Fiscal Year: 2001
    ..Such studies will provide insights into the etiology of inappropriate immune responses such as autoimmunity, and will provide a better understanding of the oncogenic activation of Src kinases in general. ..
  62. Dopamine Receptors: Characterization and Regulation
    Marc Caron; Fiscal Year: 2007
    ..the complex of receptor/arrestin engages a variety of signaling pathways including those associated with Src family kinases and components of the MAP kinase cascades...
  63. Novel Small Molecule Inhibitor of Rheumatoid Arthritis
    Jun Hayashi; Fiscal Year: 2009
    ..A subset of these compounds has been shown to be specific for Lck versus other SH2 domain containing Src family kinases with affinities for Lck in the low micromolar range...
  64. CBL PROTOONCOGENE SIGNALING MECHANISMS
    LAURIE BEITZ; Fiscal Year: 2001
    ..through the interaction of cytoplasmic tail immunoreceptor tyrosine based activation motifs (ITAMs) with SRC family kinases and the SYK tyrosine kinase...
  65. New methods for activation of kinases and kinase circuits in living cells.
    Andrei V Karginov; Fiscal Year: 2013
    ..These methods will be applied to identify the roles of different Src family kinases. These highly homologous kinases serve as a good test of the specificity of the new approaches and will ..