Human Sos1: a Guanine Nucleotide Exchange Factor for Ras that Binds to GRB2
SciencePublished 28 May 1993
Pierre Teilhard de Chardin, Jacques Camonis, Nicholas W. Gale, Linda Van Aelst, Joseph Schlessinger, Michael Wigler
Citations800
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
The results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1, a guanine nucleotide exchange factor for Ras.
Abstract
A human complementary DNA was isolated that encodes a widely expressed protein, hSos1, that is closely related to Sos, the product of the Drosophila son of sevenless gene. The hSos1 protein contains a region of significant sequence similarity to CDC25, a guanine nucleotide exchange factor for Ras from yeast. A fragment of hSos1 encoding the CDC25-related domain complemented loss of CDC25 function in yeast. This hSos1 domain specifically stimulated guanine nucleotide exchange on mammalian Ras proteins in vitro. Mammalian cells overexpressing full-length hSos1 had increased guanine nucleotide exchange activity. Thus hSos1 is a guanine nucleotide exchange factor for Ras. The hSos1 interacted with growth factor receptor-bound protein 2 (GRB2) in vivo and in vitro. This interaction was mediated by the carboxyl-terminal domain of hSos1 and the Src homology 3 (SH3) domains of GRB2. These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1.
Keywords
Biochemistry, Genetics and Molecular Biology
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