Mutation in Sos1 dominantly enhances a weak allele of the EGFR, demonstrating a requirement for sos1 in EGFR signaling and development

Dennis Z.M. Wang, Vicki E. Hammond, Helen E. Abud, Ivan Bertoncello, John W. McAvoy, David D.L. Bowtell

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63 Citations (Scopus)

Abstract

We have investigated the role of the mammalian Son of sevenless 1 (Sos1) protein in growth factor signaling in vivo by generating mice and cell lines that lacked the Sos1 protein. Homozygous null embryos were smaller than normal, died mid-gestation with cardiovascular and yolk sac defects, and their fibroblasts showed reduced mitogen-activated protein kinase activation in response to epidermal growth factor (EGF). An intercross of mice mutant for Sos1 and the EGF receptor (EGFR) demonstrated that a heterozygous mutation in Sos1 dominantly enhanced the phenotype of a weak allele of the EGFR allele (wa-2). These animals had distinctive eye defects that closely resembled those seen in mice that were null for the EGFR or its ligand, TGFα. Our findings provide the first demonstration of a functional requirement for Sos1 in growth factor signaling in vivo. They also show that the genetic test of enhancement of weak receptor allele by heterozygous mutation in one component represents a powerful tool for analyzing the ras pathway in mammals.

Original languageEnglish
Pages (from-to)309-320
Number of pages12
JournalGenes & Development
Volume11
Issue number3
DOIs
Publication statusPublished - 1 Feb 1997
Externally publishedYes

Keywords

  • EGF receptor
  • gene targeting
  • protein tyrosine kinase receptor signaling ras
  • Son of sevenless

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