Faculty Collaboration Database

Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways. Oncogene 1998 May 14;16(19):2425-34

Date

06/17/1998

Pubmed ID

9627109

DOI

10.1038/sj.onc.1201781

Scopus ID

2-s2.0-0032516236 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

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.

Author List

Sorokin A, Reed E, Nnkemere N, Dulin NO, Schlessinger J

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Calcium-Calmodulin-Dependent Protein Kinases
Cell Line
Guanine Nucleotide Exchange Factors
Humans
Insulin
Insulin Receptor Substrate Proteins
Mice
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Phosphoproteins
Phosphorylation
Platelet-Derived Growth Factor
Protein-Tyrosine Kinases
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-crk
Rats
Receptor, Insulin
Receptors, Platelet-Derived Growth Factor
Signal Transduction
Tyrosine