Epidermal growth factor regulates the exchange rate of guanine nucleotides on p21ras in fibroblasts.
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.
Buday
L
L
Imperial Cancer Research Fund, London, United Kingdom.
Downward
J
J
D000818:Animals; D001426:Bacterial Proteins; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D019833:Genistein; D006150:Guanine Nucleotides / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013301:Streptolysins / Q000494:pharmacology; D020703:ras GTPase-Activating Proteins
D001426:Bacterial Proteins; D020690:GTPase-Activating Proteins; D006150:Guanine Nucleotides; D007529:Isoflavones; D011506:Proteins; D013301:Streptolysins; D020703:ras GTPase-Activating Proteins; C025964:streptolysin O; D004815:Epidermal Growth Factor; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras)