Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor

Shuichi Okada, Jeffrey E. Pessin

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Co-immunoprecipitation of whole cell extracts demonstrated that the guanylnucleotide exchange factor SOS was associated with the small adapter proteins Grb2, CrkII, and Nck. In vitro binding indicated a similar binding affinity of SOS for all three adapter proteins but with a slightly lower K(d) for Grb2 (~2.5-fold) compared with Nck and CrkII. Insulin stimulation resulted in co-immunoprecipitation of tyrosine-phosphorylated IRS1 with Grb2 and to a lesser extent CrkII. Although Grb2 also associated with tyrosine- phosphorylated Shc, there was no detectable interaction of CrkII with Shc. In contrast, EGF stimulation resulted in the predominant co-immunoprecipitation of Grb2 with the EGF receptor, whereas CrkII primarily associated with an unidentified 120-130-kDa protein. Similar to the ability of insulin to induce the dissociation of the Grb2-SOS complex, there was a concomitant time- dependent dissociation of the CrkII-SOS and Nck-SOS complexes. However, EGF stimulation had no effect on the association state of the Grb2-SOS or the Nck-SOS complexes but did result in a time-dependent dissociation of the CrkII from SOS. Together, these data demonstrate that different cellular pools of SOS associate with different adapter proteins forming various signaling complexes, each undergoing distinct patterns of assembly/disassembly following growth factor stimulation.

Original languageEnglish (US)
Pages (from-to)25533-25538
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number41
DOIs
StatePublished - Oct 19 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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