EPIDERMAL GROWTH-FACTOR REGULATES THE EXCHANGE-RATE OF GUANINE-NUCLEOTIDES ON P21RAS IN FIBROBLASTS

被引:141
作者
BUDAY, L [1 ]
DOWNWARD, J [1 ]
机构
[1] IMPERIAL CANC RES FUND,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND
关键词
D O I
10.1128/MCB.13.3.1903
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Treatment of intact Rat-I fibroblasts with epidermal growth factor (EGF) leads to rapid activation of cellular ras-encoded proteins. By using the bacterial toxin streptolysin 0 to permeabilize these cells, it was shown that the low basal rate at which guanine nucleotides bind to, and dissociate from, ras-encoded protein in quiescent fibroblasts was greatly accelerated by EGF treatment. Nucleotide binding to other proteins was not affected. Stimulation of nucleotide exchange op ras-encoded protein required tyrosine kinase but not phospholipase activity. EGF had no effect on total GTPase-activating protein activity. Regulation of ras-encoded protein in Rat-1 fibroblasts is therefore mediated by stimulation, either directly or indirectly, of ras-encoded protein-specific guanine nucleotide exchange factors by the EGF receptor tyrosine kinase.
引用
收藏
页码:1903 / 1910
页数:8
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