CrkL

Summary

Gene Symbol: CrkL
Description: CRK like proto-oncogene, adaptor protein
Alias: crk-like protein, v-crk avian sarcoma virus CT10 oncogene homolog-like
Species: human
Products:     CrkL

Top Publications

  1. Smit L, van der Horst G, Borst J. Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors. J Biol Chem. 1996;271:8564-9 pubmed
    ..Since Cbl binds to Grb2, Crk, as well as Crk-L, we hypothesize that Cbl may affect the function of all three exchangers. ..
  2. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, et al. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J Biol Chem. 2000;275:10772-8 pubmed
    ..YXXP) motifs which, when phosphorylated, are potential binding sites for the adapter proteins c-Crk and Crk-like (CRKL). Stimulation of human embryonic kidney cells (HEK293) with HGF leads to Gab1 association with CRKL...
  3. Li L, Guris D, Okura M, Imamoto A. Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases. Mol Cell Biol. 2003;23:2883-92 pubmed
    The adapter protein Crk-Like (CrkL) can associate with the Src substrate p130(Cas) (Cas). The biological role of CrkL downstream of Cas, however, has been largely obscure...
  4. Salgia R, Pisick E, Sattler M, Li J, Uemura N, Wong W, et al. p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene. J Biol Chem. 1996;271:25198-203 pubmed
    ..In primary samples from virtually all patients with CML or Ph+ALL, the CRKL adapter protein is tyrosine phosphorylated and physically associated with p210(BCR/ABL)...
  5. Ingham R, Krebs D, Barbazuk S, Turck C, Hirai H, Matsuda M, et al. B cell antigen receptor signaling induces the formation of complexes containing the Crk adapter proteins. J Biol Chem. 1996;271:32306-14 pubmed
    ..In RAMOS cells, we found that the SH3 domains of Crk-L and Crk II bound C3G. Since C3G activates Rap, a negative regulator of the Ras pathway, Crk proteins may participate in regulation of Ras signaling by the BCR. ..
  6. Bhat A, Kolibaba K, Oda T, Ohno Jones S, Heaney C, Druker B. Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. J Biol Chem. 1997;272:16170-5 pubmed
    ..Since CRKL, an SH2, SH3 domain-containing adapter protein is known to bind directly to BCR-ABL and also binds to tyrosine-..
  7. Astier A, Manie S, Law S, Canty T, Haghayghi N, Druker B, et al. Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells. Leuk Lymphoma. 1997;28:65-72 pubmed
    b>CrkL, a cellular homologue of the v-crk oncogene, belongs to the family of adaptor proteins, containing SH2 and SH3 domains, but no catalytic domain...
  8. Koval A, Karas M, Zick Y, LeRoith D. Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. J Biol Chem. 1998;273:14780-7 pubmed
    The closely related proto-oncogene proteins CrkII and CrkL consist of one SH2 and two SH3 domains and share 60% overall homology with the highest identity within their functional domains...
  9. Senechal K, Heaney C, Druker B, Sawyers C. Structural requirements for function of the Crkl adapter protein in fibroblasts and hematopoietic cells. Mol Cell Biol. 1998;18:5082-90 pubmed
    b>Crkl is an adapter protein and phosphotyrosine-containing substrate implicated in transformation by the bcr-abl oncogene and in signaling by cytokines...

More Information

Publications105 found, 100 shown here

  1. Harkiolaki M, Gilbert R, Jones E, Feller S. The C-terminal SH3 domain of CRKL as a dynamic dimerization module transiently exposing a nuclear export signal. Structure. 2006;14:1741-53 pubmed
    b>CRKL plays essential roles in cell signaling. It consists of an N-terminal SH2 domain followed by two SH3 domains. SH2 and SH3N bind to signaling proteins, but the function of the SH3C domain has remained largely enigmatic...
  2. Cheung H, Du J, Boehm J, He F, Weir B, Wang X, et al. Amplification of CRKL induces transformation and epidermal growth factor receptor inhibitor resistance in human non-small cell lung cancers. Cancer Discov. 2011;1:608-25 pubmed publisher
    ..21 in a subset of primary lung adenocarcinomas. Here we show that CRKL, encoding for an adaptor protein, is amplified and overexpressed in non-small cell lung cancer (NSCLC) cells that ..
  3. Zhao T, Miao Z, Wang Z, Xu Y, Wu J, Liu X, et al. Overexpression of CRKL correlates with malignant cell proliferation in breast cancer. Tumour Biol. 2013;34:2891-7 pubmed publisher
    Crk-like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration...
  4. Reedquist K, Fukazawa T, Panchamoorthy G, Langdon W, Shoelson S, Druker B, et al. Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G. J Biol Chem. 1996;271:8435-42 pubmed
    ..Here we show that Cbl associates with all three forms of the human Crk protein, predominantly CrkL, following T cell receptor activation of Jurkat T cells...
  5. De Jong R, ten Hoeve J, Heisterkamp N, Groffen J. Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site. Oncogene. 1997;14:507-13 pubmed
    BCR/ABL has a causal role in Philadelphia (Ph)-chromosome positive leukemia. The SH2/SH3 adapter protein CRKL is a major substrate of the deregulated BCR/ABL tyrosine kinase and is aberrantly tyrosine-phosphorylated in Ph-positive ..
  6. Boussiotis V, Freeman G, Berezovskaya A, Barber D, Nadler L. Maintenance of human T cell anergy: blocking of IL-2 gene transcription by activated Rap1. Science. 1997;278:124-8 pubmed
    ..The adapter protein CrkL was associated with both phosphorylated Cbl and the guanidine nucleotide-releasing factor C3G, which catalyzes ..
  7. Kyono W, De Jong R, Park R, Liu Y, Heisterkamp N, Groffen J, et al. Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI). J Immunol. 1998;161:5555-63 pubmed
    Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1...
  8. Shao Y, Elly C, Liu Y. Negative regulation of Rap1 activation by the Cbl E3 ubiquitin ligase. EMBO Rep. 2003;4:425-31 pubmed
    ..Previous studies have proposed that Cbl is also a positive regulator of CrkL-C3G signalling, which leads to Rap1 activation...
  9. Senechal K, Halpern J, Sawyers C. The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. J Biol Chem. 1996;271:23255-61 pubmed
    The CRKL adaptor protein was recently identified as a substrate for the BCR-ABL tyrosine kinase in patients with chronic myelogenous leukemia, but its function is unknown...
  10. Park R, Kyono W, Liu Y, Durden D. CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling. J Immunol. 1998;160:5018-27 pubmed
    ..Glutathione-S-transferase fusion protein data demonstrate that the constitutive interaction of CBL with GRB2 and CRKL is mediated via two discrete regions of the CBL C terminus...
  11. Bhat A, Johnson K, Oda T, Corbin A, Druker B. Interactions of p62(dok) with p210(bcr-abl) and Bcr-Abl-associated proteins. J Biol Chem. 1998;273:32360-8 pubmed
    ..by p210(bcr-abl), p62(dok) is tyrosine-phosphorylated and co-immunoprecipitates with Bcr-Abl, RasGAP, and CrkL, a Src homology 2 (SH2) and SH3 domain-containing adaptor protein...
  12. Erdreich Epstein A, Liu M, Kant A, Izadi K, Nolta J, Durden D. Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages. J Leukoc Biol. 1999;65:523-34 pubmed
    ..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...
  13. Gomez T, Hamann M, McCarney S, Savoy D, Lubking C, Heldebrant M, et al. Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Nat Immunol. 2005;6:261-70 pubmed
    ..These data identify a functionally important interaction between Dyn2 and Vav1 that regulates actin reorganization and multiple signaling pathways in T lymphocytes. ..
  14. ten Hoeve J, Morris C, Heisterkamp N, Groffen J. Isolation and chromosomal localization of CRKL, a human crk-like gene. Oncogene. 1993;8:2469-74 pubmed
    ..We identified one SH2 and two SH3 domains within the 303 amino acid open reading frame of this crk-like gene, CRKL. The CRKL gene product is predicted to have a molecular mass of 36 kDa...
  15. Uemura N, Griffin J. The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration. J Biol Chem. 1999;274:37525-32 pubmed
    b>Crkl, an SH2-SH3-SH3 adapter protein, is one of the major tyrosine phosphoproteins detected in cells from patients with chronic myelogenous leukemia...
  16. Nakamura T, Komiya M, Sone K, Hirose E, Gotoh N, Morii H, et al. Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules. Mol Cell Biol. 2002;22:8721-34 pubmed
    ..Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases...
  17. Heaney C, Kolibaba K, Bhat A, Oda T, Ohno S, Fanning S, et al. Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood. 1997;89:297-306 pubmed
    b>CRKL has previously been shown to be a major tyrosine phosphorylated protein in neutrophils of patients with BCR-ABL+ chronic myelogenous leukemia and in cell lines expressing BCR-ABL CRKL and BCR-ABL form a complex as demonstrated by ..
  18. Feller S, Posern G, Voss J, Kardinal C, Sakkab D, Zheng J, et al. Physiological signals and oncogenesis mediated through Crk family adapter proteins. J Cell Physiol. 1998;177:535-52 pubmed
    ..oncogene (v-Crk) is known to induce sarcomas in chicken and its cellular homologs c-Crk I, c-Crk II, and Crk-like (CRKL) have been implicated in many signal transduction events...
  19. Park R, Izadi K, Deo Y, Durden D. Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling. Blood. 1999;94:2112-20 pubmed
    ..that FcalphaR-mediated signals modulate a multimolecular adaptor protein complex containing Grb2, Shc, SHIP, CrkL, Cbl, and SLP-76...
  20. Zhang W, Shao Y, Fang D, Huang J, Jeon M, Liu Y. Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b. J Biol Chem. 2003;278:23978-83 pubmed
    ..Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. ..
  21. Graf R, Barbero S, Keller N, Chen L, Uryu S, Schlaepfer D, et al. Src-inducible association of CrkL with procaspase-8 promotes cell migration. Cell Adh Migr. 2013;7:362-9 pubmed publisher
    ..Here we show that the cytoskeletal adaptor protein CrkL promotes caspase-8 recruitment to the peripheral spreading edge of cells, and that the catalytic domain of caspase-..
  22. Shen Q, Rahn J, Zhang J, Gunasekera N, Sun X, Shaw A, et al. MUC1 initiates Src-CrkL-Rac1/Cdc42-mediated actin cytoskeletal protrusive motility after ligating intercellular adhesion molecule-1. Mol Cancer Res. 2008;6:555-67 pubmed publisher
    ..lamellipodial and filopodial protrusions require Src family kinase and CT10 regulator of kinase like (CrkL) accompanied by the rapid formation of a Src-CrkL signaling complex at the MUC1 cytoplasmic domain...
  23. Felschow D, McVeigh M, Hoehn G, Civin C, Fackler M. The adapter protein CrkL associates with CD34. Blood. 2001;97:3768-75 pubmed
    ..By Western analysis, we identified the 39-kd protein as CrkL. In vivo, CrkL was coimmunoprecipitated with CD34 using CD34 antibodies, confirming the association between CrkL ..
  24. Peterson M, Long E. Inhibitory receptor signaling via tyrosine phosphorylation of the adaptor Crk. Immunity. 2008;29:578-88 pubmed publisher
  25. Li J, Chen Y, Chen B, Chen C, Qiu B, Zheng Z, et al. Inhibition of 32Dp210 cells harboring T315I mutation by a novel derivative of emodin correlates with down-regulation of BCR-ABL and its downstream signaling pathways. J Cancer Res Clin Oncol. 2015;141:283-93 pubmed publisher
    ..Moreover, the activation of the P210(BCR-ABL) downstream signaling pathways including CrkL, Akt/mTOR and MEK/ERK was fully suppressed by E35...
  26. Tanaka S, Chen Yoshikawa T, Kajiwara M, Menju T, Ohata K, Takahashi M, et al. Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung. Ann Thorac Surg. 2016;102:1717-1724 pubmed publisher
    ..The expression of vascular endothelial cadherin (VEC), the phosphorylation level of CrkL (pCrkL) (an exclusive target of Abl kinases), and the cytokine level were evaluated using lung tissue lysate...
  27. Tamura M, Sasaki Y, Kobashi K, Takeda K, Nakagaki T, Idogawa M, et al. CRKL oncogene is downregulated by p53 through miR-200s. Cancer Sci. 2015;106:1033-40 pubmed publisher
    ..In silico analyses of miRNA targets established the CRKL oncogene as a potential target for miR-200b/200c/429...
  28. Du J, Flynn R, Paz K, Ren H, Ogata Y, Zhang Q, et al. Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a novel biomarker in patients. Blood. 2018;: pubmed publisher
    ..cGVHD that are targetable by genetic ablation or blocking antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8 and CCL9 chemokines...
  29. Cheerathodi M, Vincent J, Ballif B. Quantitative comparison of CrkL-SH3 binding proteins from embryonic murine brain and liver: Implications for developmental signaling and the quantification of protein species variants in bottom-up proteomics. J Proteomics. 2015;125:104-11 pubmed publisher
    ..This is particularly true when molecular size information is lost as in gel-free proteomics. Crk and CrkL comprise a family of adaptor proteins that couple upstream phosphotyrosine signals to downstream effectors by ..
  30. Ghosh A, Ghosh A, Datta S, Dasgupta D, Das S, Ray S, et al. Hepatic miR-126 is a potential plasma biomarker for detection of hepatitis B virus infected hepatocellular carcinoma. Int J Cancer. 2016;138:2732-44 pubmed publisher
    ..of these two miRNAs in hepato-carcinogenesis, target genes related to cancer pathways (APAF1, APC2, CDKN2A, IRS1, CRKL, LIFR, EGR2) were verified...
  31. Zhao Y, Dong Q, Wang E. MicroRNA-320 inhibits invasion and induces apoptosis by targeting CRKL and inhibiting ERK and AKT signaling in gastric cancer cells. Onco Targets Ther. 2017;10:1049-1058 pubmed publisher
    ..By using luciferase reporter assay, we found that CRKL serves as the target of miR-320...
  32. Lin H, Chen M, Rothe K, Lorenzi M, Woolfson A, Jiang X. Selective JAK2/ABL dual inhibition therapy effectively eliminates TKI-insensitive CML stem/progenitor cells. Oncotarget. 2014;5:8637-50 pubmed
    ..Combination therapy reduces JAK2/STAT5 and CRKL activities, induces apoptosis, inhibits proliferation and colony growth, and eliminates CML LSCs in vitro...
  33. Ling P, Meyer C, Redmond L, Shui J, Davis B, Rich R, et al. Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling. J Biol Chem. 2001;276:18908-14 pubmed
    ..the adapters Nck and Crk with different kinetics, whereas it constitutively interacted with the adapters Grb2 and CrkL in Jurkat T cells...
  34. Taher T, Tjin E, Beuling E, Borst J, Spaargaren M, Pals S. c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination. J Immunol. 2002;169:3793-800 pubmed
    ..Cbl association with the Src family tyrosine kinases Fyn and Lyn, as well as with phosphatidylinositol-3 kinase and CrkL. In addition, we demonstrate that c-Cbl mediates HGF-induced ubiquitination of Met...
  35. Oda A, Wakao H, Fujihara M, Ozaki K, Komatsu N, Tanaka S, et al. Thrombopoietin and interleukin-2 induce association of CRK with STAT5. Biochem Biophys Res Commun. 2000;278:299-305 pubmed
    Crk (Crk I and II) proteins and closely related CrkL are adapters which are commonly involved in various signaling processes in various cells, and these proteins share many ligands...
  36. Guo C, Liu S, Sun M. The role of CT10 regulation of kinase-like in cancer. Future Oncol. 2014;10:2687-97 pubmed publisher
    V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family. It acts as an adaptor protein in intracellular signal transduction...
  37. Barber D, Mason J, Fukazawa T, Reedquist K, Druker B, Band H, et al. Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins. Blood. 1997;89:3166-74 pubmed
    ..Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed ..
  38. Engels N, Merchant M, Pappu R, Chan A, Longnecker R, Wienands J. Epstein-Barr virus latent membrane protein 2A (LMP2A) employs the SLP-65 signaling module. J Exp Med. 2001;194:255-64 pubmed
    ..phosphorylation of one of the two SLP-65 isoforms and complex formation between SLP-65 and the protooncoprotein CrkL (CT10 regulator of kinase like)...
  39. Tian L, Chen L, McClafferty H, Sailer C, Ruth P, Knaus H, et al. A noncanonical SH3 domain binding motif links BK channels to the actin cytoskeleton via the SH3 adapter cortactin. FASEB J. 2006;20:2588-90 pubmed
    ..Targeting of cortactin to BK channels via a novel, noncanonical SH3 domain binding motif has important implications for the coordination of BK channel function in normal physiology and disease. ..
  40. Brendel C, Scharenberg C, Dohse M, Robey R, Bates S, Shukla S, et al. Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia. 2007;21:1267-75 pubmed
    ..K562 cells were protected from imatinib and nilotinib-mediated cell death and from downregulation of P-CRKL. Moreover, photoaffinity labeling revealed interaction of both TKIs with ABCG2 at the substrate binding sites as ..
  41. Segovis C, Schoon R, Dick C, Nacusi L, Leibson P, Billadeau D. PI3K links NKG2D signaling to a CrkL pathway involved in natural killer cell adhesion, polarity, and granule secretion. J Immunol. 2009;182:6933-42 pubmed publisher
    ..We demonstrate that an interaction between the regulatory subunit of PI3K, p85, and the adaptor protein CrkL is required for efficient NKG2D-mediated cellular cytotoxicity...
  42. Wang Y, Dong X, Hu B, Wang X, Wang Q, Wang W. The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL. Biomed Pharmacother. 2016;80:311-321 pubmed publisher
    ..ZEB1 and Crk-like adapter protein (CRKL), as novel targets of miR-429 and direct regulators of the actin cytoskeleton were identified...
  43. Carpenter V, Chen Y, Dolat L, Valdivia R. The Effector TepP Mediates Recruitment and Activation of Phosphoinositide 3-Kinase on Early Chlamydia trachomatis Vacuoles. mSphere. 2017;2: pubmed publisher
    ..of type I IFN genes, and recruitment of class I phosphoinositide 3-kinases (PI3K) and signaling adaptor protein CrkL to nascent pathogen-containing vacuoles (inclusions)...
  44. Aiello F, Guszczynski T, Li W, Hixon J, Jiang Q, Hodge D, et al. IL-7-induced phosphorylation of the adaptor Crk-like and other targets. Cell Signal. 2018;47:131-141 pubmed publisher
    ..pathways related to survival, proliferation and gene expression, respectively, and increased the phosphorylation of CrkL, a member of a family of adaptors including the highly homologous Crk isoforms CrkII and CrkI, important in ..
  45. Ribon V, Hubbell S, Herrera R, Saltiel A. The product of the cbl oncogene forms stable complexes in vivo with endogenous Crk in a tyrosine phosphorylation-dependent manner. Mol Cell Biol. 1996;16:45-52 pubmed
    ..These results indicate that Crk binds to c-Cbl in a tyrosine phosphorylation-dependent manner, suggesting a physiological role for the Crk-c-Cbl complex in Bcr-Abl tyrosine phosphorylation-mediated transformation. ..
  46. Gesbert F, Garbay C, Bertoglio J. Interleukin-2 stimulation induces tyrosine phosphorylation of p120-Cbl and CrkL and formation of multimolecular signaling complexes in T lymphocytes and natural killer cells. J Biol Chem. 1998;273:3986-93 pubmed
    ..factor for T lymphocytes, was found to induce tyrosine phosphorylation of the proto-oncogene products p120-Cbl and CrkL in IL-2-dependent cell lines...
  47. Bengoa Alonso A, Artigas López M, Moreno Igoa M, Cattalli C, Hernández Charro B, Ramos Arroyo M. Delineation of a recognizable phenotype for the recurrent LCR22-C to D/E atypical 22q11.2 deletion. Am J Med Genet A. 2016;170:1485-94 pubmed publisher
    ..Genotype-phenotype analysis of the patients indicates that CRKL and MAPK1 genes play an important role as causative factors for the main clinical features of the syndrome...
  48. Luo H, Wan X, Wu Y, Wu J. Cross-linking of EphB6 resulting in signal transduction and apoptosis in Jurkat cells. J Immunol. 2001;167:1362-70 pubmed
    ..Our results show that EphB6 has important functions in T cells, and it can transduce signals into the cells via proteins it associates with. ..
  49. Ye Z, Ma G, Zhao Y, Xiao Y, Zhan Y, Jing C, et al. miR-429 inhibits migration and invasion of breast cancer cells in vitro. Int J Oncol. 2015;46:531-8 pubmed publisher
    ..We identified ZEB1 and CRKL as potential targets of miR-429 by analyzing combined results from in silico search and global expression array of ..
  50. Ishida Y, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Ogawa K, et al. Pharmacokinetics and pharmacodynamics of dasatinib in the chronic phase of newly diagnosed chronic myeloid leukemia. Eur J Clin Pharmacol. 2016;72:185-93 pubmed publisher
    ..The dasatinib concentration required to inhibit 50 % of the CrkL (CT10 regulator of kinase like) phosphorylation in bone marrow CD34+ cells (half maximal (50 %) inhibitory ..
  51. Giacomelli M, Kumar R, Soresina A, Tamassia N, Lorenzini T, Moratto D, et al. Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions. J Allergy Clin Immunol. 2016;138:229-240.e3 pubmed publisher
    Partial DiGeorge syndrome (pDGS) is caused by deletion of the 22q11.2 region. Within this region lies CrK-like (CRKL), a gene encoding an adapter protein belonging to the Crk family that is involved in the signaling cascade of IL-2, ..
  52. Benz P, Laban H, Zink J, Günther L, Walter U, Gambaryan S, et al. Vasodilator-Stimulated Phosphoprotein (VASP)-dependent and -independent pathways regulate thrombin-induced activation of Rap1b in platelets. Cell Commun Signal. 2016;14:21 pubmed publisher
    ..Interaction of VASP and Crkl was investigated by co-immunoprecipitation, confocal microscopy, and pull-down assays using Crkl domains expressed ..
  53. Cai H, Qin X, Yang C. Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl-JAK/STAT Signaling Pathways. J Cell Biochem. 2017;118:3381-3390 pubmed publisher
    ..inhibits the phosphorylation expression of Bcr/Abl, STAT5, JAK2, and STAT3 and downstream molecules including p-CrkL, Mcl-1, Bcl-XL, and Bcl-2 proteins in K562 cells...
  54. Salgia R, Uemura N, Okuda K, Li J, Pisick E, Sattler M, et al. CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells. J Biol Chem. 1995;270:29145-50 pubmed
    ..In primary neutrophils from patients with CML, the major novel tyrosine-phosphorylated protein is CRKL, an SH2-SH3-SH3 linker protein which has an overall homology of 60% to CRK, the human homologue of the v-crk ..
  55. Oda A, Ochs H, Lasky L, Spencer S, Ozaki K, Fujihara M, et al. CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk. Blood. 2001;97:2633-9 pubmed
    ..Platelets express an SH2-SH3 adapter molecule, CrkL, that can directly associate with paxillin, which is localized in podosomes...
  56. Seo J, Suenaga A, Hatakeyama M, Taiji M, Imamoto A. Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop. Mol Cell Biol. 2009;29:3076-87 pubmed publisher
    The adapter protein CRKL is required for the normal development of multiple tissues that rely on fibroblast growth factor 8 (FGF8). The precise role of CRKL in receptor signaling has been unclear, however...
  57. Dong G, Kalifa R, Nath P, Gelkop S, Isakov N. TCR crosslinking promotes Crk adaptor protein binding to tyrosine-phosphorylated CD3? chain. Biochem Biophys Res Commun. 2017;488:541-546 pubmed publisher
    ..Phospho-CD3? binding is selective and is mediated by the three types of Crk, including CrkI, CrkII, and CrkL, but not by other SH2 domain-containing adaptor proteins, such as Grb2, GRAP and Nck...
  58. Guo C, Zhao D, Zhang Q, Liu S, Sun M. miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition. Sci Rep. 2018;8:2375 pubmed publisher
    Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying ..
  59. Wang J, Park I, Groopman J. Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C. Blood. 2000;95:2505-13 pubmed
    ..These studies further delineate the molecular pathways mediating hematopoietic progenitor migration and response to an essential chemokine, SDF-1alpha. (Blood. 2000;95:2505-2513) ..
  60. Ballif B, Arnaud L, Arthur W, Guris D, Imamoto A, Cooper J. Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Curr Biol. 2004;14:606-10 pubmed
    ..Of these, the Crk-family proteins (CrkL, CrkI, and CrkII ), bind significant quantities of Dab1 when embryonic cortical neurons are exposed to Reelin...
  61. Gangenahalli G, Singh V, Verma Y, Gupta P, Sharma R, Chandra R, et al. Three-dimensional structure prediction of the interaction of CD34 with the SH3 domain of Crk-L. Stem Cells Dev. 2005;14:470-7 pubmed
    ..Our results suggest that the interaction of the cytoplasmic tail of CD34 with the shallow proline-rich motif-binding groove of Crk-L is essential for the function of CD34 in stem cell development. ..
  62. Simara P, Peterkova M, Stejskal S, Potěšilová M, Koutna I, Racil Z, et al. BCR-ABL activity measured by 50% inhibitory concentration for imatinib, p-CrkL/CrkL ratio or p-CrkL ratio in CD34+ cells of patients with chronic myeloid leukemia does not predict treatment response. Leuk Lymphoma. 2012;53:1627-9 pubmed publisher
  63. Han B, Luan L, Xu Z, Wu B. Clinical significance and biological roles of CRKL in human bladder carcinoma. Tumour Biol. 2014;35:4101-6 pubmed publisher
    b>CRKL encodes an adaptor protein that has been recently reported to be overexpressed in various cancers and associate with the malignant behavior of cancer cells...
  64. Lin F, Chengyao X, Qingchang L, Qianze D, Enhua W, Yan W. CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway. Mol Carcinog. 2015;54 Suppl 1:E35-44 pubmed publisher
    b>CRKL is recently defined as a new oncogene, which plays a role in the lung cancer progression. However, the potential mechanism of CRKL in human non-small cell lung cancer cell invasion is obscure...
  65. Han G, Wu D, Yang Y, Li Z, Zhang J, Li C. CrkL meditates CCL20/CCR6-induced EMT in gastric cancer. Cytokine. 2015;76:163-169 pubmed publisher
    In recent years, Crk-like adapter protein (CrkL) has been identified as a key regulator in the epithelial-to-mesenchymal transition (EMT)...
  66. van Dijk T, van den Akker E, Amelsvoort M, Mano H, Lowenberg B, von Lindern M. Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells. Blood. 2000;96:3406-13 pubmed
    ..Dok-1 was demonstrated to bind to the SH2 domains of several signaling molecules activated by SCF, including Abl, CrkL, SHIP, and PLCgamma-1, but not those of Vav and Shc...
  67. Sanders M, Ampasala D, Basson M. DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and migration on collagen IV. J Biol Chem. 2009;284:27-35 pubmed publisher
    We observed previously that combined small interfering RNAs (siRNAs) targeting CrkII and CrkL, known activators of guanine nucleotide exchange factor DOCK1, strongly inhibit Caco-2 intestinal epithelial cell spreading and migration on ..
  68. Uemura N, Salgia R, Li J, Pisick E, Sattler M, Griffin J. The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins. Leukemia. 1997;11:376-85 pubmed
    ..In primary leukemic neutrophils from patients with CML, the major tyrosine phosphorylated protein is CRKL, an SH2-SH3-SH3 adapter protein which has an overall homology of 60% to CRK, the human homologue of the v-crk ..
  69. Heikkinen L, Kazlauskas A, Melen K, Wagner R, Ziegler T, Julkunen I, et al. Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling. J Biol Chem. 2008;283:5719-27 pubmed publisher
    ..Screening of a comprehensive human SH3 phage library revealed the N-terminal SH3 of Crk and CrkL as the preferred binding partners...
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    The adapter protein CrkL is required for regulating the malignant potential of human cancers...
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    ..The association of Crk and Abl suggests that Abl could play a role in v-Crk and Crk-I transformation and that normal Abl function may be partly mediated through bound adapter molecules. ..
  72. Arevalo J, Pereira D, Yano H, Teng K, Chao M. Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation. J Biol Chem. 2006;281:1001-7 pubmed
    ..A reassembled complex of ARMS/Kidins220 and CrkL, an upstream component of the C3G-Rap1-MAP kinase cascade, is SH3-dependent...
  73. Mintz P, Cardo Vila M, Ozawa M, Hajitou A, Rangel R, Guzman Rojas L, et al. An unrecognized extracellular function for an intracellular adapter protein released from the cytoplasm into the tumor microenvironment. Proc Natl Acad Sci U S A. 2009;106:2182-7 pubmed publisher
    ..random peptide libraries in tumor-bearing mice, we uncovered a direct, specific, and functional interaction between CRKL, an adapter protein [with Src homology 2 (SH2)- and SH3-containing domains], and the plexin-semaphorin-integrin ..
  74. López Rivera E, Liu Y, Verbitsky M, Anderson B, Capone V, Otto E, et al. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome. N Engl J Med. 2017;376:742-754 pubmed publisher
    ..In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects...
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    ..LPCs than either therapy alone or both in vitro and in humanized Ph+ALL mice by reducing phospho-CrKL and phospho-JAK2 activities at the molecular level...
  76. Ahmad S, Alsayed Y, Druker B, Platanias L. The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. J Biol Chem. 1997;272:29991-4 pubmed
    ..induces rapid and transient tyrosine phosphorylation of the Src homology 2/Src homology 3 (SH2/SH3)-containing CrkL adaptor protein in a time- and dose-dependent manner...
  77. Schulze H, Ballmaier M, Welte K, Germeshausen M. Thrombopoietin induces the generation of distinct Stat1, Stat3, Stat5a and Stat5b homo- and heterodimeric complexes with different kinetics in human platelets. Exp Hematol. 2000;28:294-304 pubmed
    ..Stat5 complexes bound to labeled DNA with a fast kinetic followed by Stat3 and Stat1. The adapter protein CrkL is present in DNA-bound Stat5 complexes and predominantly bound to Stat5b...
  78. Brenner B, Kadel S, Birle A, Linderkamp O. L-selectin tyrosine phosphorylates cbl and induces association of tyrosine-phosphorylated cbl with crkl and grb2. Biochem Biophys Res Commun. 2001;282:41-7 pubmed
    ..There is an activation induced association of tyrosine phosphorylated Cbl with Grb2 and CrkL, respectively, but not CrkII...
  79. Huang J, Umehara H, Inoue H, Tabassam F, Okazaki T, Kono T, et al. Differential interaction of Cbl with Grb2 and CrkL in CD2-mediated NK cell activation. Mol Immunol. 2000;37:1057-65 pubmed
    ..Cbl-Grb2 and Cbl-CrkL interactions have been implicated in T cell and B cell receptor, and cytokine receptor signaling...
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    ..In this study, we demonstrated that DOCK2 bound to CrkL, which is present exclusively in hematopoietic cells both in vivo and in vitro, and we also found that 2 separate ..
  81. Mazzu Y, Hu Y, Soni R, Mojica K, Qin L, Agius P, et al. miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells. Cancer Res. 2017;77:5728-5740 pubmed publisher
    ..proteomic analysis of miR-193b-target networks identified novel direct targets, including CRK-like proto-oncogene (CRKL) and focal adhesion kinase (FAK). miR-193b was found to regulate FAK-SRC-CRKL signaling through CRKL and FAK...
  82. Yokote K, Hellman U, Ekman S, Ronnstrand L, Saito Y, Heldin C, et al. Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins. Oncogene. 1998;16:1229-39 pubmed
    ..of partial amino acid sequences of the purified proteins indicated that they were identical to CrkI, CrkII and CrkL respectively...
  83. Schaeper U, Gehring N, Fuchs K, Sachs M, Kempkes B, Birchmeier W. Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol. 2000;149:1419-32 pubmed
    ..with downstream substrates, we developed a modified yeast two-hybrid assay and identified PI(3)K, Shc, Shp2, and CRKL as interaction partners of Gab1...
  84. Grumbach I, Mayer I, Uddin S, Lekmine F, Majchrzak B, Yamauchi H, et al. Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells. Br J Haematol. 2001;112:327-36 pubmed
    ..The CrkL adaptor protein interacts directly with the BCR-ABL fusion protein that causes the malignant transformation and is ..
  85. Wu C, Lai C, Mobley W. Nerve growth factor activates persistent Rap1 signaling in endosomes. J Neurosci. 2001;21:5406-16 pubmed
    ..basis for Rap1 activation, we examined complexes containing C3G, a guanine nucleotide exchange factor for Rap1, and CrkL, an adapter protein known to influence Rap1 signaling...
  86. Aten T, Redmond M, Weaver S, Love C, Joy R, Lapp A, et al. Tyrosine phosphorylation of the orphan receptor ESDN/DCBLD2 serves as a scaffold for the signaling adaptor CrkL. FEBS Lett. 2013;587:2313-8 pubmed publisher
    ..screen to identify substrates of the Src family of tyrosine kinases (SFKs) whose phosphorylation promotes CrkL-SH2 binding identified the known Crk-associated substrate (Cas) of Src as well as the orphan receptor endothelial ..
  87. Yang X, Lv W, Shi R, Cheng S, Zhang J, Xu Z. The clinical implications of Crk-like adaptor protein expression in papillary thyroid microcarcinoma. Tumour Biol. 2014;35:12435-40 pubmed publisher
    ..Crk-like (CrkL) adaptor protein was identified in the development of many carcinomas...
  88. He Y, Kapoor A, Cook S, Liu S, Xiang Y, Rao C, et al. The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge. J Cell Sci. 2011;124:2153-64 pubmed publisher
    ..Furthermore, Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge...
  89. George B, Fan Q, Dlugos C, Soofi A, Zhang J, Verma R, et al. Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis. Kidney Int. 2014;85:1382-1394 pubmed publisher
    ..As Crk1/2-null mice developed and aged normally, we tested whether the Crk1/2 paralog, CrkL, functionally complements Crk1/2 in a podocyte-specific context...
  90. Park T, Koptyra M, Curran T. Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL). J Biol Chem. 2016;291:26273-26290 pubmed
    CT10 regulator of kinase (Crk) and Crk-like (CrkL) are the cellular counterparts of the viral oncogene v-Crk Elevated levels of Crk and CrkL have been observed in many human cancers; inhibition of Crk and CrkL expression reduced the tumor-..
  91. Nolz J, Nacusi L, Segovis C, Medeiros R, Mitchell J, Shimizu Y, et al. The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1. J Cell Biol. 2008;182:1231-44 pubmed publisher
    ..activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL-C3G exchange complex...
  92. Hantschel O, Warsch W, Eckelhart E, Kaupe I, Grebien F, Wagner K, et al. BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. Nat Chem Biol. 2012;8:285-93 pubmed publisher
    ..Thus, attempts to pharmacologically target STAT5 in BCR-ABL(+) diseases need to focus on STAT5 itself. ..