Insulin and epidermal growth factor receptors regulate distinct pools of Grb2-SOS in the control of Ras activation

Steven B. Waters, Dong Chen, Aimee W. Kao, Shuichi Okada, Kathleen H. Holt, Jeffrey E. Pessin

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Insulin and epidermal growth factor (EGF) stimulate a rapid but transient increase in the amount of GTP bound to Ras that returns to the basal GDP-bound state within 10-30 min. Although insulin stimulation resulted in a dissociation of the Grb2·SOS complex, EGF did not affect the Grb2·SOS complex but instead induced dissociation of Grb2-SOS from tyrosine- phosphorylated Shc. The dissociation of Grb2-SOS from Shc was not due to dephosphorylation as Shc remained persistently tyrosine-phosphorylated during this time. Furthermore, there was no decrease in the extent of insulin receptor substrate 1, insulin receptor, or EGF receptor tyrosine phosphorylation. Surprisingly, however, despite the EGF-induced decrease in the amount of Grb2-SOS bound to Shc, the extent of Grb2 associated with Shc remained constant, and there was a concomitant increase in the amount of SOS associated with Grb2. In addition, after the insulin-stimulated dissociation of Grb2 from SOS, EGF treatment induced the reassociation of the Grb2·SOS complex. Quantitative immunoprecipitation demonstrated that only a small fraction of the total cellular pool of Grb2 was associated with SOS. Similarly, only a small fraction of SOS and Grb2 were co-immunoprecipitated with Shc. Together, these data suggest the presence of distinct Grb2-SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine-phosphorylated Shc.

Original languageEnglish (US)
Pages (from-to)18224-18230
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number30
DOIs
StatePublished - Aug 10 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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