Human Sos1: A guanine nucleotide exchange factor for ras that binds to GRB2

Journal Article · Fri May 28 00:00:00 EDT 1993 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.8493579· OSTI ID:6180196

Chardin, P ^[1]; Camonis, J; Gale, N W; Aelst, L Van; Wigler, M H; Bar-Sagi, D ^[2]; Schlessinger, J ^[3]

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1. Institut de Pharmacologie Moleculaire et Cellulaire du CNRS 660, Valbonne (France)
2. Cold Spring Harbor Lab., NY (United States)
3. New York Univ., New York (United States)

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. 42 refs., 5 figs.

• OSTI ID: 6180196
• Journal Information: Science (Washington, D.C.); (United States), Vol. 260:5112; ISSN 0036-8075
• Country of Publication: United States
• Language: English

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