Gene Symbol: Crk
Description: v-crk avian sarcoma virus CT10 oncogene homolog
Alias: Crk-I, Crk-II, Crk-III, Crk3, CrkIII, Crko, c-Crk, p38, adapter molecule crk, CT-10 related kinase 3, avian sarcoma virus CT10 (v-crk) oncogene homolog, proto-oncogene c-crk, v-crk sarcoma virus CT10 oncogene-like protein
Species: mouse
Products:     Crk

Top Publications

  1. Mayer B, Hamaguchi M, Hanafusa H. A novel viral oncogene with structural similarity to phospholipase C. Nature. 1988;332:272-5 pubmed
    ..This virus encodes a protein, p47gag-crk, that has blocks of sequence similarity to the amino-terminal, non-catalytic region of the non-receptor class of ..
  2. Ogawa S, Toyoshima H, Kozutsumi H, Hagiwara K, Sakai R, Tanaka T, et al. The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3Y1 cells. Oncogene. 1994;9:1669-78 pubmed
    We have isolated the mouse c-crk cDNA from a mouse liver cDNA library. It encodes 304 amino acids and consists mainly of SH2/SH3 regions...
  3. Nguyen J, Turck C, Cohen F, Zuckermann R, Lim W. Exploiting the basis of proline recognition by SH3 and WW domains: design of N-substituted inhibitors. Science. 1998;282:2088-92 pubmed
    ..The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity. ..
  4. Zheng J, Machida K, Antoku S, Ng K, Claffey K, Mayer B. Proteins that bind the Src homology 3 domain of CrkI have distinct roles in Crk transformation. Oncogene. 2010;29:6378-89 pubmed publisher
    The v-Crk oncogene product consists of two protein interaction modules, a Src homology 2 (SH2) domain and a Src homology 3 (SH3) domain...
  5. Sung B, Yeo M, Oh H, Song W. v-Crk induces Rac-dependent membrane ruffling and cell migration in CAS-deficient embryonic fibroblasts. Mol Cells. 2008;25:131-7 pubmed
    b>Crk-associated substrate (CAS) is a focal adhesion protein that is involved in integrin signaling and cell migration. CAS deficiency reduces the migration and spreading of cells, both of which are processes mediated by Rac activation...
  6. Matsuki T, Pramatarova A, Howell B. Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis. J Cell Sci. 2008;121:1869-75 pubmed publisher
    ..This enhancement is blocked by reducing expression of Crk family proteins, adaptor molecules that interact with Dab1 in a tyrosine phosphorylation-dependent manner...
  7. Park T, Curran T. Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway. J Neurosci. 2008;28:13551-62 pubmed publisher
    ..b>Crk and Crk-like (CrkL) have been proposed to interact with tyrosine phosphorylated Dab1 to mediate downstream events ..
  8. Antoku S, Mayer B. Distinct roles for Crk adaptor isoforms in actin reorganization induced by extracellular signals. J Cell Sci. 2009;122:4228-38 pubmed publisher
    b>Crk family adaptors, consisting of Src homology 2 (SH2) and SH3 protein-binding domains, mediate assembly of protein complexes in signaling...
  9. George B, Verma R, Soofi A, Garg P, Zhang J, Park T, et al. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. J Clin Invest. 2012;122:674-92 pubmed publisher
    ..In humans, focal adhesion kinase and Cas phosphorylation - markers of focal adhesion complex-mediated Crk-dependent signaling - was induced in minimal change disease and membranous nephropathy, but not focal segmental ..

More Information


  1. Hallock P, Xu C, Park T, Neubert T, Curran T, Burden S. Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes Dev. 2010;24:2451-61 pubmed publisher
    ..of two tyrosine residues in the C-terminal domain of Dok-7, which leads to recruitment of two adapter proteins: Crk and Crk-L...
  2. Park T, Boyd K, Curran T. Cardiovascular and craniofacial defects in Crk-null mice. Mol Cell Biol. 2006;26:6272-82 pubmed
    The Crk adaptor protein, which is encoded by two splice variants termed CrkI and CrkII, contains both SH2 and SH3 domains but no catalytic region...
  3. Tosello Trampont A, Kinchen J, Brugnera E, Haney L, Hengartner M, Ravichandran K. Identification of two signaling submodules within the CrkII/ELMO/Dock180 pathway regulating engulfment of apoptotic cells. Cell Death Differ. 2007;14:963-72 pubmed
    ..10 (CT10) regulator of kinase (Crk)II, CED-5/180 kDa protein downstream of chicken tumor virus no...
  4. Cipres A, Abassi Y, Vuori K. Abl functions as a negative regulator of Met-induced cell motility via phosphorylation of the adapter protein CrkII. Cell Signal. 2007;19:1662-70 pubmed
    ..Taken together, these results demonstrate that the Abl tyrosine kinase functions as a negative regulator of Met-induced cell migration, and that it does so by inducing CrkII phosphorylation at the site Y221. ..
  5. Yeo M, Sung B, Oh H, Park Z, Marcantonio E, Song W. Focal adhesion targeting of v-Crk is essential for FAK phosphorylation and cell migration in mouse embryo fibroblasts deficient src family kinases or p130CAS. J Cell Physiol. 2008;214:604-13 pubmed
    We examined the consequences of v-Crk expression in mouse embryo fibroblasts deficient Src family kinases or p130CAS...
  6. Fathers K, Rodrigues S, Zuo D, Murthy I, Hallett M, Cardiff R, et al. CrkII transgene induces atypical mammary gland development and tumorigenesis. Am J Pathol. 2010;176:446-60 pubmed publisher
    The v-Crk protein was originally isolated as the oncogene fusion product of the CT10 chicken retrovirus. Cellular homologues of v-Crk include Crk, which encodes two alternatively spliced proteins (CrkI and CrkII), and CrkL...
  7. Lee W, Cosio G, Ireton K, Grinstein S. Role of CrkII in Fcgamma receptor-mediated phagocytosis. J Biol Chem. 2007;282:11135-43 pubmed
    ..DOCK180 associates with the adaptor protein Crk, which mediates recruitment of the GEF to sites of tyrosine phosphorylation...
  8. Sorenson C. Interaction of bcl-2 with Paxillin through its BH4 domain is important during ureteric bud branching. J Biol Chem. 2004;279:11368-74 pubmed
    ..Therefore, these data suggest that the interaction of bcl-2 with paxillin plays an important role during nephrogenesis. ..
  9. 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 ..
  10. Au Yeung B, Levin S, Zhang C, Hsu L, Cheng D, Killeen N, et al. A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity. Nat Immunol. 2010;11:1085-92 pubmed publisher
    ..Our results indicate Zap70 is a likely therapeutic target. ..
  11. Ojaniemi M, Martin S, Dolfi F, Olefsky J, Vuori K. The proto-oncogene product p120(cbl) links c-Src and phosphatidylinositol 3'-kinase to the integrin signaling pathway. J Biol Chem. 1997;272:3780-7 pubmed
    ..These observations suggest that Cbl serves as a docking protein and may transduce signals to downstream signaling pathways following integrin-mediated cell adhesion in macrophages. ..
  12. Nagaike K, Kawaguchi M, Takeda N, Fukushima T, Sawaguchi A, Kohama K, et al. Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice. Am J Pathol. 2008;173:1464-75 pubmed publisher
    ..These findings indicate that Hai-1/Spint1 has critical roles in the regulated keratinization of the epidermis and hair development. ..
  13. Donaldson L, Gish G, Pawson T, Kay L, Forman Kay J. Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide. Proc Natl Acad Sci U S A. 2002;99:14053-8 pubmed
    On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221 site...
  14. Hamilton B, Smith D, Mueller K, Kerrebrock A, Bronson R, van Berkel V, et al. The vibrator mutation causes neurodegeneration via reduced expression of PITP alpha: positional complementation cloning and extragenic suppression. Neuron. 1997;18:711-22 pubmed
    ..The vibrator phenotype is suppressed in one intercross. We performed a complete genome scan and mapped a major suppressor locus (Mvb-1) to proximal chromosome 19. ..
  15. Kashiwa A, Yoshida H, Lee S, Paladino T, Liu Y, Chen Q, et al. Isolation and characterization of novel presenilin binding protein. J Neurochem. 2000;75:109-16 pubmed
    ..immunohistochemical studies and cell fractionation analysis show that PBP redistributes from cytoplasm to membranes in the presence of PS. In addition, PBP is deficient in the soluble fraction of sporadic AD brains. ..
  16. Prosser S, Sorokina E, Pratt P, Sorokin A. CrkIII: a novel and biologically distinct member of the Crk family of adaptor proteins. Oncogene. 2003;22:4799-806 pubmed
    ..Currently comprising four members, v-Crk, CrkI, CrkII and Crk-like protein, we have introduced a fifth member, CrkIII. Cloned by the CORT technique, CrkIII is identical in sequence to CrkII until the second of its two SH3 domains, ..
  17. Imaizumi T, Araki K, Miura K, Araki M, Suzuki M, Terasaki H, et al. Mutant mice lacking Crk-II caused by the gene trap insertional mutagenesis: Crk-II is not essential for embryonic development. Biochem Biophys Res Commun. 1999;266:569-74 pubmed
    b>Crk family adapter proteins including Crk-II, Crk-I, and Crk-L consist mostly of SH2 and SH3 domains...
  18. Gout I, Dhand R, Hiles I, Fry M, Panayotou G, Das P, et al. The GTPase dynamin binds to and is activated by a subset of SH3 domains. Cell. 1993;75:25-36 pubmed
  19. Huang Y, Magdaleno S, Hopkins R, Slaughter C, Curran T, Keshvara L. Tyrosine phosphorylated Disabled 1 recruits Crk family adapter proteins. Biochem Biophys Res Commun. 2004;318:204-12 pubmed
    ..Mass spectrometric analysis of bound proteins revealed that Crk family adapter proteins selectively associated with this phosphorylation site...
  20. Toyo oka K, Shionoya A, Gambello M, Cardoso C, Leventer R, Ward H, et al. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003;34:274-85 pubmed
    ..3 deletions. ..
  21. Yamaguchi A, Urano T, Goi T, Feig L. An Eps homology (EH) domain protein that binds to the Ral-GTPase target, RalBP1. J Biol Chem. 1997;272:31230-4 pubmed
    ..In addition, Reps1 has the capacity to form a complex with the SH3 domains of the adapter proteins Crk and Grb2, which may link Reps1 to an EGF-responsive tyrosine kinase...
  22. Xue Y, Yuwen T, Zhu F, Skrynnikov N. Role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets. 1. NMR and MD characterization of the complex between the c-Crk N-SH3 domain and the peptide Sos. Biochemistry. 2014;53:6473-95 pubmed publisher
    ..we investigated the binding of the peptide Sos (PPPVPPRRRR), which serves as a minimal model for an IDP, to the c-Crk N-terminal SH3 domain...
  23. Ishida N, Oritani K, Shiraga M, Yoshida H, Kawamoto S, Ujiie H, et al. Differential effects of a novel IFN-zeta/limitin and IFN-alpha on signals for Daxx induction and Crk phosphorylation that couple with growth control of megakaryocytes. Exp Hematol. 2005;33:495-503 pubmed
    ..In addition, the antisense oligonucleotides against Crk and Daxx, downstream molecules of Tyk2, greatly rescued the IFN-zeta/limitin- and IFN-alpha-induced reduction of ..
  24. LUPU F, Burnett J, Eggenschwiler J. Cell cycle-related kinase regulates mammalian eye development through positive and negative regulation of the Hedgehog pathway. Dev Biol. 2018;434:24-35 pubmed publisher
    ..These results indicate that CCRK functions in eye development by both positively and negatively regulating the Hh pathway, and they reveal distinct requirements for Hh signaling in patterning and morphogenesis of the eyes. ..
  25. Yingling J, Toyo oka K, Wynshaw Boris A. Miller-Dieker syndrome: analysis of a human contiguous gene syndrome in the mouse. Am J Hum Genet. 2003;73:475-88 pubmed
  26. Liu J, Deyoung S, Hwang J, O Leary E, Saltiel A. The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport. J Biol Chem. 2003;278:36754-62 pubmed
    ..Like c-Cbl, Cbl-b associates constitutively with CAP and interacts with Crk upon insulin stimulation...
  27. Qiu Z, Cang Y, Goff S. Abl family tyrosine kinases are essential for basement membrane integrity and cortical lamination in the cerebellum. J Neurosci. 2010;30:14430-9 pubmed publisher
    ..Together, these results provide compelling evidence that Abl and Arg play key redundant roles in BM maintenance and cortical lamination in the cerebellum. ..
  28. Feng L, Cooper J. Dual functions of Dab1 during brain development. Mol Cell Biol. 2009;29:324-32 pubmed publisher
    ..on tyrosine, it activates Akt and provides a scaffold for assembling signaling complexes, including the paralogous Crk and CrkL adaptors. The roles of Akt and Dab1 complexes during development have been unclear...
  29. Sparks A, Hoffman N, McConnell S, Fowlkes D, Kay B. Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins. Nat Biotechnol. 1996;14:741-4 pubmed
    ..The isolation of entire repertoires of modular domain-containing proteins will prove invaluable in genome analysis and in bringing new targets into drug discovery programs. ..
  30. Oneyama C, Hikita T, Nada S, Okada M. Functional dissection of transformation by c-Src and v-Src. Genes Cells. 2008;13:1-12 pubmed publisher
    ..These findings demonstrate that c-Src has the potential to induce cell transformation, but it requires coordination with an additional pathway(s) to promote tumor progression in vivo. ..
  31. Hermanto U, Zong C, Li W, Wang L. RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002;22:2345-65 pubmed
    ..and MAPK pathways was unaffected, IGF-I-inducible beta1 integrin-associated kinase activity and association of Crk with p130(CAS) were significantly inhibited by RACK1 overexpression...
  32. Huang Y, Clarke F, Karimi M, Roy N, Williamson E, Okumura M, et al. CRK proteins selectively regulate T cell migration into inflamed tissues. J Clin Invest. 2015;125:1019-32 pubmed publisher
    ..Using conditional knockout mice, we found that T cells lacking the adaptor proteins CRK and CRK-like (CRKL) exhibit reduced integrin-dependent adhesion, chemotaxis, and diapedesis...
  33. Sathyamurthy A, Yin D, Barik A, Shen C, Bean J, Figueiredo D, et al. ERBB3-mediated regulation of Bergmann glia proliferation in cerebellar lamination. Development. 2015;142:522-32 pubmed publisher
    ..These observations identify a crucial role for ERBB3 in cerebellar lamination and reveal a novel mechanism that regulates BG development. ..
  34. Liu J, Kimura A, Baumann C, Saltiel A. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. Mol Cell Biol. 2002;22:3599-609 pubmed
    ..but not an APS/Y(618)F mutant facilitated the tyrosine phosphorylation of coexpressed Cbl and its association with Crk upon insulin stimulation...
  35. Miura A, Sajan M, Standaert M, Bandyopadhyay G, Kahn C, Farese R. Insulin substrates 1 and 2 are corequired for activation of atypical protein kinase C and Cbl-dependent phosphatidylinositol 3-kinase during insulin action in immortalized brown adipocytes. Biochemistry. 2004;43:15503-9 pubmed required for insulin-stimulated glucose transport and has been found to function upstream of both PI3K/aPKC and Crk during thiazolidinedione action in 3T3/L1 adipocytes [Miura et al. (2003) Biochemistry 42, 14335]...
  36. Yano M, Hayakawa Yano Y, Mele A, Darnell R. Nova2 regulates neuronal migration through an RNA switch in disabled-1 signaling. Neuron. 2010;66:848-58 pubmed publisher
    ..Thus, Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease, and development. ..
  37. Yokoyama N, Malbon C. Dishevelled-2 docks and activates Src in a Wnt-dependent manner. J Cell Sci. 2009;122:4439-51 pubmed publisher
    ..Activated Src, in turn, enhances Wnt activation of the canonical pathway. We show that Dvl2 and beta-catenin are crucially important substrates for tyrosine phosphorylation in the canonical Wnt/beta-catenin pathway. ..
  38. Sorokin A, Reed E. Insulin stimulates the tyrosine dephosphorylation of docking protein p130cas (Crk-associated substrate), promoting the switch of the adaptor protein crk from p130cas to newly phosphorylated insulin receptor substrate-1. Biochem J. 1998;334 ( Pt 3):595-600 pubmed
    The docking protein p130(cas) (Crk-associated substrate) forms a stable complex with the adaptor protein CrkII in a tyrosine-phosphorylation-dependent manner...
  39. Scaife R, Langdon W. c-Cbl localizes to actin lamellae and regulates lamellipodia formation and cell morphology. J Cell Sci. 2000;113 Pt 2:215-26 pubmed
    ..By immunofluorescence microscopy we have determined that c-Cbl co-localizes with the adaptor protein Crk to submembranous actin lamellae in NIH 3T3 fibroblasts and that c-Cbl's actin localization requires specific SH3-..
  40. Standaert M, Sajan M, Miura A, Bandyopadhyay G, Farese R. Requirements for pYXXM motifs in Cbl for binding to the p85 subunit of phosphatidylinositol 3-kinase and Crk, and activation of atypical protein kinase C and glucose transport during insulin action in 3T3/L1 adipocytes. Biochemistry. 2004;43:15494-502 pubmed
    Cbl is phosphorylated by the insulin receptor and reportedly functions within the flotillin/CAP/Cbl/Crk/C3G/TC10 complex during insulin-stimulated glucose transport in 3T3/L1 adipocytes...
  41. Oh H, Kim H, Shin B, Lee K, Yeo M, Song W. Interaction of crk with Myosin-1c participates in fibronectin-induced cell spreading. Int J Biol Sci. 2013;9:778-91 pubmed publisher
    We previously reported a novel interaction between v-Crk and myosin-1c, and demonstrated that this interaction is essential for cell migration, even in the absence of p130CAS...
  42. Schwartz B, Marks M, Wittler L, Werber M, Währisch S, Nordheim A, et al. SRF is essential for mesodermal cell migration during elongation of the embryonic body axis. Mech Dev. 2014;133:23-35 pubmed publisher
    ..Thus, the primary role for SRF in the nascent mesoderm during elongation of the embryonic body axis is the activation of a migratory program, which is a prerequisite for axis extension. ..
  43. Fathers K, Bell E, Rajadurai C, Cory S, Zhao H, Mourskaia A, et al. Crk adaptor proteins act as key signaling integrators for breast tumorigenesis. Breast Cancer Res. 2012;14:R74 pubmed
    CT10 regulator of kinase (Crk) adaptor proteins (CrkI, CrkII and CrkL) play a role in integrating signals for migration and invasion of highly malignant breast cancer cell lines...
  44. Wu X, Knudsen B, Feller S, Zheng J, Sali A, Cowburn D, et al. Structural basis for the specific interaction of lysine-containing proline-rich peptides with the N-terminal SH3 domain of c-Crk. Structure. 1995;3:215-26 pubmed
    ..factor C3G bind much more strongly to the N-terminal Src homology 3 domain (SH3-N) of the proto-oncogene product c-Crk than to other SH3 domains...
  45. Fecchi K, Volonte D, Hezel M, Schmeck K, Galbiati F. Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells. FASEB J. 2006;20:705-7 pubmed
    ..Taken together, these results indicate that flotillin-1 and caveolin-3 may regulate muscle energy metabolism through the spatial and temporal segregation of key components of the insulin signaling. ..
  46. Koval A, Blakesley V, Roberts C, Zick Y, LeRoith D. Interaction in vitro of the product of the c-Crk-II proto-oncogene with the insulin-like growth factor I receptor. Biochem J. 1998;330 ( Pt 2):923-32 pubmed
    The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein...
  47. Mitra P, Zheng X, Czech M. RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by insulin. J Biol Chem. 2004;279:37431-5 pubmed
    ..These data are consistent with the hypothesis that CAP, Cbl iso-forms, and CrkII are not required components of insulin signaling to GLUT4 transporters. ..
  48. Odai H, Sasaki K, Hanazono Y, Ueno H, Tanaka T, Miyagawa K, et al. c-Cbl is inducibly tyrosine-phosphorylated by epidermal growth factor stimulation in fibroblasts, and constitutively tyrosine-phosphorylated and associated with v-Src in v-src-transformed fibroblasts. Jpn J Cancer Res. 1995;86:1119-26 pubmed
    ..These findings strongly suggest that c-Cbl is implicated in a wide variety of signal transduction pathways, including those of EGF receptor and Src protein, as well as in the signaling pathways of hematopoietic cells. ..
  49. Ng K, Yin T, Machida K, Wu Y, Mayer B. Phosphorylation of Dok1 by Abl family kinases inhibits CrkI transforming activity. Oncogene. 2015;34:2650-9 pubmed publisher
    The Crk SH2/SH3 adaptor and the Abl nonreceptor tyrosine kinase were first identified as oncoproteins, and both can induce tumorigenesis when overexpressed or mutationally activated...
  50. Koptyra M, Park T, Curran T. Crk and CrkL are required for cell transformation by v-fos and v-ras. Mol Carcinog. 2016;55:97-104 pubmed publisher
    b>Crk and CrkL are SH2- and SH3-containing cytosolic adaptor proteins that can induce anchorage-independent growth of fibroblasts. Crk and CrkL play key roles in maintaining cytoskeletal integrity, cell motility and migration...
  51. Austgen K, Johnson E, Park T, Curran T, Oakes S. The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. Nat Cell Biol. 2011;14:87-92 pubmed publisher
    ..We discovered that the principal component of the purified pro-apoptotic activity is the proto-oncoprotein CRK (CT10-regulated kinase), an adaptor protein with no known catalytic activity...
  52. Ribon V, Saltiel A. Insulin stimulates tyrosine phosphorylation of the proto-oncogene product of c-Cbl in 3T3-L1 adipocytes. Biochem J. 1997;324 ( Pt 3):839-45 pubmed
    ..phosphorylation, c-Cbl specifically associates with fusion proteins containing the Src homology 2 (SH2) domains of Crk and the Fyn tyrosine kinase, but not with fusion proteins containing the SH2 domains of either the p85 subunit of ..
  53. Margolis B, Silvennoinen O, Comoglio F, Roonprapunt C, Skolnik E, Ullrich A, et al. High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. Proc Natl Acad Sci U S A. 1992;89:8894-8 pubmed
    ..kinase fyn and the mouse homologue of phospholipase C-gamma 1, whereas two genes encoded proteins similar to v-crk and NCK. We also isolated the gene for GRB-7, which encodes a protein of 535 amino acids...
  54. Roselli S, Wallez Y, Wang L, Vervoort V, Pasquale E. The SH2 domain protein Shep1 regulates the in vivo signaling function of the scaffolding protein Cas. Cell Signal. 2010;22:1745-52 pubmed publisher
    ..These tyrosine-phosphorylated motifs represent docking sites for the Crk adaptor, linking Cas to the downstream Rac1 and Rap1 GTPases to regulate cell adhesion and actin cytoskeleton ..
  55. Ishibe S, Joly D, Zhu X, Cantley L. Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol Cell. 2003;12:1275-85 pubmed
    ..These experiments reveal that paxillin-dependent ERK activation at sites of cell-matrix interaction is critical for HGF-stimulated epithelial morphogenesis. ..
  56. Chiang S, Hwang J, Legendre M, Zhang M, Kimura A, Saltiel A. TCGAP, a multidomain Rho GTPase-activating protein involved in insulin-stimulated glucose transport. EMBO J. 2003;22:2679-91 pubmed
    ..Thus, TCGAP may act as a downstream effector of TC10 in the regulation of insulin-stimulated glucose transport. ..
  57. Huang J, Sakai R, Furuichi T. The docking protein Cas links tyrosine phosphorylation signaling to elongation of cerebellar granule cell axons. Mol Biol Cell. 2006;17:3187-96 pubmed
    b>Crk-associated substrate (Cas) is a tyrosine-phosphorylated docking protein that is indispensable for the regulation of the actin cytoskeletal organization and cell migration in fibroblasts...
  58. Weinstein D, Dobrenis K, Birge R. Targeted expression of an oncogenic adaptor protein v-Crk potentiates axonal growth in dorsal root ganglia and motor neurons in vivo. Brain Res Dev Brain Res. 1999;116:29-39 pubmed a cellular model for neuronal differentiation, we showed that pheochromocytoma (PC12) cells expressing v-Crk, an oncogenic form of the SH2/SH3-containing c-Crk adaptor protein, potentiates axonal growth and prolongs nerve ..
  59. Amsen D, Kruisbeek A, Bos J, Reedquist K. Activation of the Ras-related GTPase Rap1 by thymocyte TCR engagement and during selection. Eur J Immunol. 2000;30:2832-41 pubmed
    ..We find that Rap1 and proposed regulators of Rap1 (the proto-oncogene product Cbl, Crk family adaptor proteins, and the Rap1 guanine nucleotide exchange factor C3G) are expressed at equivalent levels in ..
  60. 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
    ..Thus, Crk1/2 and CrkL are physically linked, functionally complement each other during podocyte foot process spreading, and together are required for developing typical foot process architecture. ..
  61. Woodring P, Litwack E, O Leary D, Lucero G, Wang J, Hunter T. Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension. J Cell Biol. 2002;156:879-92 pubmed
    ..The reciprocal regulation between F-actin and the c-Abl tyrosine kinase may provide a self-limiting mechanism in the control of actin cytoskeleton dynamics. ..
  62. Lawrenson I, Wimmer Kleikamp S, Lock P, Schoenwaelder S, Down M, Boyd A, et al. Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 2002;115:1059-72 pubmed
  63. Nishiya N, Kiosses W, Han J, Ginsberg M. An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells. Nat Cell Biol. 2005;7:343-52 pubmed
    ..These findings establish a mechanism for the spatial localization of Rac activity to enhance cell migration. ..
  64. 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 ..
  65. Ribon V, Printen J, Hoffman N, Kay B, Saltiel A. A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes. Mol Cell Biol. 1998;18:872-9 pubmed
    ..After insulin-dependent tyrosine phosphorylation, c-Cbl specifically associates with endogenous c-Crk and Fyn. These results suggest a role for tyrosine-phosphorylated c-Cbl in 3T3-L1 adipocyte activation by insulin...
  66. De Jong R, Haataja L, Voncken J, Heisterkamp N, Groffen J. Tyrosine phosphorylation of murine Crkl. Oncogene. 1995;11:1469-74 pubmed
    ..Expression of both crkl and the related crk was ubiquitous in the adult...
  67. Snouffer A, Brown D, Lee H, Walsh J, Lupu F, Norman R, et al. Cell Cycle-Related Kinase (CCRK) regulates ciliogenesis and Hedgehog signaling in mice. PLoS Genet. 2017;13:e1006912 pubmed publisher
  68. Oda T, Kujovich J, Reis M, Newman B, Druker B. Identification and characterization of two novel SH2 domain-containing proteins from a yeast two hybrid screen with the ABL tyrosine kinase. Oncogene. 1997;15:1255-62 pubmed
    ..Shd was tyrosine phosphorylated in COS-7 cells co-transfected with Shd and c-Abl or Bcr-Abl. These results suggest that Shd may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. ..
  69. Sorokin A, Reed E, Nnkemere N, Dulin N, Schlessinger J. Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways. Oncogene. 1998;16:2425-34 pubmed
    We have studied the involvement of murine c-Crk, an SH2/SH3 containing adaptor protein, in signaling pathways stimulated by different receptor tyrosine kinases...