Biology:Adapter molecule crk

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.[1]

The CRK protein participates in the Reelin signaling cascade downstream of DAB1.[2][3]

Function

Adapter molecule crk is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. This protein has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described.[4]

Crk together with CrkL participates in the Reelin signaling cascade downstream of DAB1.[2][3]

v-Crk, a transforming oncoprotein from avian sarcoma viruses, is a fusion of viral "gag" protein with the SH2 and SH3 domains of cellular Crk.[5] The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase domains, but capable of stimulating phosphorylation of tyrosines in cells.[6]

Crk should not be confused with Src, which also has cellular (c-Src) and viral (v-Src) forms and is involved in some of the same signaling pathways but is a protein tyrosine-kinase.

Interactions

CRK (gene) has been shown to interact with:


See also

  • CrkL, "Crk-like" protein

References

  1. "Association of the v-crk oncogene product with phosphotyrosine-containing proteins and protein kinase activity.". Proc Natl Acad Sci U S A 87 (7): 2638–42. 1990. doi:10.1073/pnas.87.7.2638. PMID 1690891. Bibcode1990PNAS...87.2638M. 
  2. 2.0 2.1 "Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis". J. Cell Sci. 121 (Pt 11): 1869–75. June 2008. doi:10.1242/jcs.027334. PMID 18477607. 
  3. 3.0 3.1 "Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway". J. Neurosci. 28 (50): 13551–62. December 2008. doi:10.1523/JNEUROSCI.4323-08.2008. PMID 19074029. 
  4. "Entrez Gene: CRK v-crk sarcoma virus CT10 oncogene homolog (avian)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1398. 
  5. Tetsuya Nakamoto; Ryuichi Sakai; Keiya Ozawa; Yoshio Yazaki; Hisamaru Hirai (1996). "Direct Binding of C-terminal Region of p130Graphic to SH2 and SH3 Domains of Src Kinase". J. Biol. Chem. 271 (15): 8959–8965. doi:10.1074/jbc.271.15.8959. PMID 8621540. 
  6. "A novel viral oncogene with structural similarity to phospholipase C". Nature 332 (6161): 272–5. March 1988. doi:10.1038/332272a0. PMID 2450282. Bibcode1988Natur.332..272M. 
  7. "The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity". Cancer Res. 64 (20): 7455–63. 2004. doi:10.1158/0008-5472.CAN-04-1574. PMID 15492270. 
  8. "P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein involved in cell spreading". Mol. Biol. Cell 15 (2): 787–800. 2004. doi:10.1091/mbc.E03-09-0689. PMID 14657239. 
  9. 9.0 9.1 9.2 "Differential regulation of cell motility and invasion by FAK". J. Cell Biol. 160 (5): 753–67. 2003. doi:10.1083/jcb.200212114. PMID 12615911. 
  10. 10.0 10.1 "Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)-CrkII-DOCK180 pathway". J. Biol. Chem. 276 (29): 27090–7. 2001. doi:10.1074/jbc.M102284200. PMID 11369773. 
  11. "Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST". J. Biol. Chem. 274 (6): 3811–8. 1999. doi:10.1074/jbc.274.6.3811. PMID 9920935. 
  12. 12.0 12.1 12.2 "Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts". J. Cell Biol. 144 (5): 1019–31. 1999. doi:10.1083/jcb.144.5.1019. PMID 10085298. 
  13. "Inhibition of p130cas tyrosine phosphorylation by calyculin A". J. Leukoc. Biol. 63 (5): 631–5. 1998. doi:10.1002/jlb.63.5.631. PMID 9581808. 
  14. "Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades". J. Biol. Chem. 274 (21): 14893–901. 1999. doi:10.1074/jbc.274.21.14893. PMID 10329689. 
  15. "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 95 (8): 2505–13. 2000. doi:10.1182/blood.V95.8.2505. PMID 10753828. 
  16. "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. 273 (7): 3986–93. 1998. doi:10.1074/jbc.273.7.3986. PMID 9461587. 
  17. "CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2". Oncogene 14 (19): 2331–8. 1997. doi:10.1038/sj.onc.1201074. PMID 9178909. 
  18. 18.0 18.1 "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins". J. Biol. Chem. 271 (24): 14468–72. 1996. doi:10.1074/jbc.271.24.14468. PMID 8662907. 
  19. "Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins". Biochim. Biophys. Acta 1452 (2): 179–87. 1999. doi:10.1016/S0167-4889(99)00133-0. PMID 10559471. 
  20. "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane". Mol. Cell. Biol. 16 (4): 1770–6. 1996. doi:10.1128/MCB.16.4.1770. PMID 8657152. 
  21. "The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R". J. Biol. Chem. 270 (25): 15341–7. 1995. doi:10.1074/jbc.270.25.15341. PMID 7797522. 
  22. 9614078 "Phosphotyrosine interactome of the ErbB-receptor kinase family". Mol. Syst. Biol. 1 (1): E1–E13. 2005. doi:10.1038/msb4100012. PMID 16729043. 
  23. "Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor". J. Biol. Chem. 273 (27): 17186–91. 1998. doi:10.1074/jbc.273.27.17186. PMID 9642287. 
  24. "The beta-subunit of the hepatocyte growth factor/scatter factor (HGF/SF) receptor phosphorylates and associates with CrkII: expression of CrkII enhances HGF/SF-induced mitogenesis". Biochem. J. 350 (3): 925–32. 2000. doi:10.1042/0264-6021:3500925. PMID 10970810. 
  25. 25.0 25.1 "Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor". J. Biol. Chem. 271 (41): 25533–8. 1996. doi:10.1074/jbc.271.41.25533. PMID 8810325. 
  26. "The insulin-like growth factor I receptor-induced interaction of insulin receptor substrate-4 and Crk-II". Endocrinology 142 (5): 1835–40. 2001. doi:10.1210/endo.142.5.8135. PMID 11316748. 
  27. "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction". J. Biol. Chem. 273 (24): 14780–7. 1998. doi:10.1074/jbc.273.24.14780. PMID 9614078. 
  28. "The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". Oncogene 17 (15): 1893–901. 1998. doi:10.1038/sj.onc.1202108. PMID 9788432. 
  29. "Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase". Mol. Cell. Biol. 19 (2): 1359–68. 1999. doi:10.1128/MCB.19.2.1359. PMID 9891069. 
  30. "Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling". J. Biol. Chem. 276 (22): 18908–14. 2001. doi:10.1074/jbc.M101485200. PMID 11279207. 
  31. "A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation". EMBO J. 20 (13): 3437–46. 2001. doi:10.1093/emboj/20.13.3437. PMID 11432831. 
  32. "Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes". J. Exp. Med. 184 (4): 1365–75. 1996. doi:10.1084/jem.184.4.1365. PMID 8879209. 
  33. "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G". J. Biol. Chem. 273 (11): 6446–51. 1998. doi:10.1074/jbc.273.11.6446. PMID 9497377. 
  34. 34.0 34.1 "Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation". Biochem. Biophys. Res. Commun. 270 (1): 28–33. 2000. doi:10.1006/bbrc.2000.2374. PMID 10733900. 
  35. "Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins". Oncogene 16 (10): 1229–39. 1998. doi:10.1038/sj.onc.1201641. PMID 9546424. 
  36. "Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling". EMBO J. 21 (17): 4571–82. 2002. doi:10.1093/emboj/cdf446. PMID 12198159. 
  37. "C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3443–7. 1994. doi:10.1073/pnas.91.8.3443. PMID 7512734. Bibcode1994PNAS...91.3443T. 
  38. "GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2". J. Biol. Chem. 278 (36): 34641–53. 2003. doi:10.1074/jbc.M304594200. PMID 12819203. 
  39. "Characterization of a brain-specific Rho GTPase-activating protein, p200RhoGAP". J. Biol. Chem. 278 (6): 4151–9. 2003. doi:10.1074/jbc.M207789200. PMID 12454018. 
  40. "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochem. Biophys. Res. Commun. 278 (1): 167–74. 2000. doi:10.1006/bbrc.2000.3760. PMID 11071869. https://zenodo.org/record/1229524. 

Further reading

External links