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PMID: 8441421 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular and cellular biology ·Vol. 13 ·No. 3 ·1993-03-00 ·Pages 1903-10

Buday L, Downward J

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.

Related Genes
ras
MeSH Terms
Animals Bacterial Proteins Cell Membrane Permeability/drug effects Dose-Response Relationship, Drug Epidermal Growth Factor/pharmacology Fibroblasts/drug effects,metabolism GTPase-Activating Proteins Genistein Guanine Nucleotides/metabolism Isoflavones/pharmacology Protein-Tyrosine Kinases/drug effects,metabolism Proteins/metabolism Proto-Oncogene Proteins p21(ras)/drug effects,metabolism Rats Streptolysins/pharmacology ras GTPase-Activating Proteins
Chemicals
Bacterial Proteins GTPase-Activating Proteins Guanine Nucleotides Isoflavones Proteins Streptolysins ras GTPase-Activating Proteins streptolysin O Epidermal Growth Factor Genistein Protein-Tyrosine Kinases Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Buday L
Imperial Cancer Research Fund, London, United Kingdom.
Downward J
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30 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.3.1903-1910.1993
Published
1993-03-00
Pages
1903-10
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359504
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.3.1903-1910.1993 PMC Full Text View journal details
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