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 language | English |
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Pages (from-to) | 309-320 |
Number of pages | 12 |
Journal | Genes & Development |
Volume | 11 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Feb 1997 |
Externally published | Yes |
Keywords
- EGF receptor
- gene targeting
- protein tyrosine kinase receptor signaling ras
- Son of sevenless