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Mol Cell Biol. 1993 March; 13(3): 1903-1910

Epidermal growth factor regulates the exchange rate of guanine nucleotides on p21ras in fibroblasts.

L Buday and J Downward

Imperial Cancer Research Fund, London, United Kingdom.

ABSTRACT

Treatment of intact Rat-1 fibroblasts with epidermal growth factor (EGF) leads to rapid activation of cellular ras-encoded proteins. By using the bacterial toxin streptolysin O 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 on 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.

Mol Cell Biol. 1993 March; 13(3): 1903-1910




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