Transforming activity of ras proteins translocated to the plasma membrane by a myristoylation sequence from the src gene product.
Ras p21 proteins exert their biological functions when associated to the inner surface of the plasma membrane. This association is mediated by a lipid molecule which is covalently attached to the protein by a thioester bond through a cysteine at residue 186, at the carboxy end of the molecule. Deletion or substitution of the critical Cys186 residue of the Harvey-ras protein leads to ras-p21 mutants lacking the ability to translocate to the membrane and devoid of transforming activity (Willumsen et al., 1984a, 1984b). We have been able to regenerate both localization to the plasma membrane as well as transforming activity of such mutant ras p21 proteins by fusion of the amino-terminal 15 residues of the v-p60src protein, responsible for the covalent binding of myristic acid and its membrane association. Thus, while translocation to the plasma membrane is necessary for function of the transforming Harvey-ras p21 protein, it appears to be independent of a specific membrane insertion mechanism.
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Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Pennington
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Lacal
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D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000503:physiopathology*; D011905:Genes, ras; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D019814:Myristic Acid; D009227:Myristic Acids / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src); D013329:Structure-Activity Relationship
D008565:Membrane Proteins; D009227:Myristic Acids; D011518:Proto-Oncogene Proteins; D019814:Myristic Acid; D016392:Proto-Oncogene Proteins pp60(c-src)