HUMAN SOS1 - A GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR RAS THAT BINDS TO GRB2

被引:741
作者
CHARDIN, P
CAMONIS, JH
GALE, NW
VANAELST, L
SCHLESSINGER, J
WIGLER, MH
BARSAGI, D
机构
[1] COLD SPRING HARBOR LAB,1 BUNGTOWN RD,BOX 100,COLD SPRING HARBOR,NY 11724
[2] CNRS,INST PHARMACOL MOLEC & CELLULAIRE,F-06560 VALBONNE,FRANCE
[3] NYU MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016
关键词
D O I
10.1126/science.8493579
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1338 / 1343
页数:6
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