| First Author | Sorokin A | Year | 1998 |
| Journal | Oncogene | Volume | 16 |
| Issue | 19 | Pages | 2425-34 |
| PubMed ID | 9627109 | Mgi Jnum | J:85285 |
| Mgi Id | MGI:2673753 | Doi | 10.1038/sj.onc.1201781 |
| Citation | Sorokin A, et al. (1998) Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways. Oncogene 16(19):2425-34 |
| abstractText | We have studied the involvement of murine c-Crk, an SH2/SH3 containing adaptor protein, in signaling pathways stimulated by different receptor tyrosine kinases. We show here that c-Crk is associated with components of insulin- and PDGF-dependent signaling pathways. Insulin treatment of murine myoblast cells induces the formation of stable complex of endogenous c-Crk with insulin receptor substrate-1 (IRS-1) mediated via the SH2 domain of Crk. The ligand dependent physical association of c-Crk with IRS-1 is direct. However IRS-1 is also co-precipitated with c-Crk from quiescent L6 cells. The association of IRS-1 with c-Crk in quiescent cells is probably not direct since Far Western blot analysis did not reveal the binding of neither SH2 domain nor amino-terminal SH3 domain of c-Crk to IRS-1 from unstimulated cells. We also show that PDGF treatment of murine myoblast cells induces association of c-Crk with the PDGF receptor and tyrosine phosphorylation of c-Crk. Overexpression of c-Crk enhanced insulin- but not PDGF-induced activation of MAP kinases when compared to parental cell lines. Thus, the formation of the direct IRS-1/Crk complex appears to be crucial for Crk-mediated insulin-induced activation of MAP kinase, whereas Crk is probably involved in other PDGF-induced responses. These data provide support to the hypothesis that insulin and PDGF employ different mechanisms for activation of MAP kinase cascade. |
