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Crk  -  v-crk avian sarcoma virus CT10 oncogene...

Rattus norvegicus

Synonyms: Adapter molecule crk, Crko, Proto-oncogene c-Crk, p38
 
 
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Disease relevance of Crk

  • Isoflurane preconditioning induces neuroprotection against ischemia via activation of P38 mitogen-activated protein kinases [1].
  • P38 mitogen-activated protein kinase inhibition attenuates ischemia-reperfusion injury of the rat liver [2].
  • These results suggest that Kuppfer cells can reverse liver fibrosis via the expression of MMPs mainly through P38 pathway [3].
  • Between the ages of P7-P38, P2 receptor damage lowers ganglion concentration of an acidic membrane glycoprotein designated as A1, with an apparent M(r) of 64-67 kDa and a pI of 4.8-5.2 P2 receptor damage also lowers ganglion concentrations of GAP-43 [4].
  • Recombinant constitutively active adenovirus (Ad)-MKK6 and-MKK7 increased TNF-alpha production in KCs with activation of P38 and JNK without any change by Ad-MEK1 delivery [5].
 

High impact information on Crk

  • With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105 [6].
  • Tumor necrosis factor alpha-induced PPAR-beta phosphorylation and expression was evaluated by metabolic labeling and by using specific P38 inhibitors [7].
  • Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling [8].
  • Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype [9].
  • This v-Crk-dependent formation of microvilli was suppressed by inhibitors of Rho-associated kinase, and the activity of RhoA was elevated by coexpression of c-Crk-II and ERMs in 3Y1 cells [10].
 

Biological context of Crk

  • To further explore the role of Crk in NGF-induced PC-12 cell differentiation, we found that both NGF and epidermal growth factor stimulate the tyrosine phosphorylation of endogenous Crk II [11].
  • This interaction is mediated by the SH2 domain of Crk and can be inhibited with a phosphopeptide containing the Crk-SH2 binding motif [11].
  • The signaling adaptor protein Crk has been shown to regulate cell motility, but its precise role is still under investigation [10].
  • The Crk family of adaptor proteins participate in diverse signaling pathways that regulate growth factor-induced proliferation, anchorage-dependent DNA synthesis, and cytoskeletal reorganization, important for cell adhesion and motility [12].
  • c-SRC mediates neurite outgrowth through recruitment of Crk to the scaffolding protein Sin/Efs without altering the kinetics of ERK activation [13].
 

Anatomical context of Crk

 

Associations of Crk with chemical compounds

  • These results suggest that Crk may be involved in regulation of cell motility by a hyaluronic acid-dependent mechanism through an association with ERMs [10].
  • Moreover, hormone stimulation enhanced the specific association of Crk proteins with the tyrosine-phosphorylated p130Cas, the major phosphotyrosine-containing protein in cells transformed with v-Crk [11].
  • CONCLUSION: beta cells contain the SH2-containing adapter protein Crk, which undergoes glucose-induced association with p130Cas [16].
  • The binding of two guanine nucleotide exchange factors, Sos and C3G, to Crk and CRKL indicates that Ras or related proteins likely play a role in signaling through Crk family proteins [17].
  • It was found in complexes with many signaling proteins, including phosphoinositol (PtdIns) 3-kinase (EC 2.7.1.137), Cbl, GRB2, p130Cas and Crk [18].
 

Physical interactions of Crk

  • Whereas previous studies have shown that Crk SH2 binding to paxillin is critical for cell adhesion and migration, our data show that the phosphorylation cycle of c-Crk II determines its dynamic interaction with paxillin, thereby regulating turnover of multiprotein complexes, a critical aspect of cytoskeletal plasticity and actin dynamics [12].
 

Other interactions of Crk

  • Moreover, Crk together with Dock180 were present at the filopodial tips of beta1B-integrin-expressing cells, and there was a prominent Rac1 activation [19].
  • However, both forms could associate with Csk and Crk [20].
  • Collectively, the focal adhesion-dependent p130Cas/Crk/Pyk2/c-Src-mediated pathway is selectively involved in ET-induced JNK activation in cardiomyocytes [21].
  • The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk [22].
  • Overlay analyses and affinity chromatography with glutathione S-transferase (GST) fusion proteins of Src homology-3 (SH3) domains showed direct binding of the Src but not the Crk SH3 domain to p58gag [23].
 

Analytical, diagnostic and therapeutic context of Crk

  • In contrast, little or no rescue was observed in the retinas of those RCS dystrophic rats when RPE cell transplantation was performed at P38, P43 and P48 [24].
  • P38 mitogen-activated protein kinase inhibition attenuates pulmonary inflammatory response in a rat cardiopulmonary bypass model [25].
  • According to Western blotting analysis and immunohistochemical and morphological observations, laminin not only retains SMCs in a contractile state but also possibly stimulates cells to transform a synthetic to a contractile phenotype at an early stage, mediated by P38 MAPK signal transduction [26].
  • A higher degree of expression of all the three classes of MAPK, i.e. JNK, P38 MAP kinases and P-extracellular signal regulated kinases (ERKs) can be seen in kidneys subjected to ischemia/reperfusion insult [27].

References

  1. Isoflurane preconditioning induces neuroprotection against ischemia via activation of P38 mitogen-activated protein kinases. Zheng, S., Zuo, Z. Mol. Pharmacol. (2004) [Pubmed]
  2. P38 mitogen-activated protein kinase inhibition attenuates ischemia-reperfusion injury of the rat liver. Kobayashi, M., Takeyoshi, I., Yoshinari, D., Matsumoto, K., Morishita, Y. Surgery (2002) [Pubmed]
  3. Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells. Sakaida, I., Hironaka, K., Terai, S., Okita, K. Life Sci. (2003) [Pubmed]
  4. Alterations in geniculate ganglion proteins following fungiform receptor damage. Lasiter, P.S., Bulcourf, B.B. Brain Res. Dev. Brain Res. (1995) [Pubmed]
  5. Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Shen, J., Sakaida, I., Uchida, K., Terai, S., Okita, K. Life Sci. (2005) [Pubmed]
  6. 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. Minegishi, M., Tachibana, K., Sato, T., Iwata, S., Nojima, Y., Morimoto, C. J. Exp. Med. (1996) [Pubmed]
  7. Peroxisome proliferator-activated receptor-beta signaling contributes to enhanced proliferation of hepatic stellate cells. Hellemans, K., Michalik, L., Dittie, A., Knorr, A., Rombouts, K., De Jong, J., Heirman, C., Quartier, E., Schuit, F., Wahli, W., Geerts, A. Gastroenterology (2003) [Pubmed]
  8. Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling. Abassi, Y.A., Vuori, K. EMBO J. (2002) [Pubmed]
  9. Phosphorylation of tyrosine residues 31 and 118 on paxillin regulates cell migration through an association with CRK in NBT-II cells. Petit, V., Boyer, B., Lentz, D., Turner, C.E., Thiery, J.P., Vallés, A.M. J. Cell Biol. (2000) [Pubmed]
  10. Crk associates with ERM proteins and promotes cell motility toward hyaluronic acid. Tsuda, M., Makino, Y., Iwahara, T., Nishihara, H., Sawa, H., Nagashima, K., Hanafusa, H., Tanaka, S. J. Biol. Chem. (2004) [Pubmed]
  11. Nerve growth factor stimulates the tyrosine phosphorylation of endogenous Crk-II and augments its association with p130Cas in PC-12 cells. Ribon, V., Saltiel, A.R. J. Biol. Chem. (1996) [Pubmed]
  12. Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates nerve growth factor-induced cell spreading and morphogenesis. Escalante, M., Courtney, J., Chin, W.G., Teng, K.K., Kim, J.I., Fajardo, J.E., Mayer, B.J., Hempstead, B.L., Birge, R.B. J. Biol. Chem. (2000) [Pubmed]
  13. c-SRC mediates neurite outgrowth through recruitment of Crk to the scaffolding protein Sin/Efs without altering the kinetics of ERK activation. Yang, L.T., Alexandropoulos, K., Sap, J. J. Biol. Chem. (2002) [Pubmed]
  14. Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins. Khwaja, A., Hallberg, B., Warne, P.H., Downward, J. Oncogene (1996) [Pubmed]
  15. Signaling adaptor protein v-Crk activates Rho and regulates cell motility in 3Y1 rat fibroblast cell line. Tsuda, M., Tanaka, S., Sawa, H., Hanafusa, H., Nagashima, K. Cell Growth Differ. (2002) [Pubmed]
  16. Glucose stimulates the association of Crk with p130Cas in pancreatic beta cells. Lee, T.N., Gold, G., Workman, R., Cook, C.A., Konrad, R.J. Pancreas (2004) [Pubmed]
  17. Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways. Feller, S.M., Knudsen, B., Hanafusa, H. Oncogene (1995) [Pubmed]
  18. Ruk is ubiquitinated but not degraded by the proteasome. Verdier, F., Valovka, T., Zhyvoloup, A., Drobot, L.B., Buchman, V., Waterfield, M., Gout, I. Eur. J. Biochem. (2002) [Pubmed]
  19. Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation. Gustavsson, A., Yuan, M., Fällman, M. J. Biol. Chem. (2004) [Pubmed]
  20. Depolarization-induced tyrosine phosphorylation of paxillin in PC12h cells. Khan, M.A., Okumura, N., Okada, M. Eur. J. Biochem. (1996) [Pubmed]
  21. Selective involvement of p130Cas/Crk/Pyk2/c-Src in endothelin-1-induced JNK activation. Kodama, H., Fukuda, K., Takahashi, E., Tahara, S., Tomita, Y., Ieda, M., Kimura, K., Owada, K.M., Vuori, K., Ogawa, S. Hypertension (2003) [Pubmed]
  22. Discrimination between phosphotyrosine-mediated signaling properties of conventional and neuronal Shc adapter molecules. Nakamura, T., Komiya, M., Gotoh, N., Koizumi, S., Shibuya, M., Mori, N. Oncogene (2002) [Pubmed]
  23. c-Src association with and phosphorylation of p58gag, a membrane- and microfilament-associated retroviral Gag-like protein in a xenotransplantable rat mammary tumor. Huang, J., Zhang, B.T., Li, Y., Mayer, B., Carraway, K.L., Carraway, C.A. Oncogene (1999) [Pubmed]
  24. Optimal conditions for long-term photoreceptor cell rescue in RCS rats: the necessity for healthy RPE transplants. Li, L., Turner, J.E. Exp. Eye Res. (1991) [Pubmed]
  25. P38 mitogen-activated protein kinase inhibition attenuates pulmonary inflammatory response in a rat cardiopulmonary bypass model. Dong, X., Liu, Y., Du, M., Wang, Q., Yu, C.T., Fan, X. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. (2006) [Pubmed]
  26. Effects of extracellular matrix on phenotype modulation and MAPK transduction of rat aortic smooth muscle cells in vitro. Qin, H., Ishiwata, T., Wang, R., Kudo, M., Yokoyama, M., Naito, Z., Asano, G. Exp. Mol. Pathol. (2000) [Pubmed]
  27. Attenuation of ischemia/reperfusion induced MAP kinases by N-acetyl cysteine, sodium nitroprusside and phosphoramidon. Mehta, A., Sekhon, C.P., Giri, S., Orak, J.K., Singh, A.K. Mol. Cell. Biochem. (2002) [Pubmed]
 
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