title: Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation.
abstract: p60src, the transforming protein kinase of Rous sarcoma virus, contains the 14-carbon saturated fatty acid, myristic acid, linked through an amide bond to the alpha-amino group of its NH2-terminal glycine residue. Myristic acid is known to be attached to four other eukaryotic proteins. In each case the fatty acid is also linked through an amide bond to an NH2-terminal glycine. We have used oligonucleotide-directed mutagenesis to examine the amino acid specificity of the enzyme that myristoylates the NH2 terminus of these proteins. Replacement of the NH2-terminal glycine in p60src with either alanine or glutamic acid prevented myristoylation completely. This indicates that the myristoylating enzyme may have an absolute specificity for glycine. Strikingly, neither nonmyristoylated mutant src protein induced morphological transformation of infected cells, even though wild-type levels of phosphorylation of cellular proteins on tyrosine were observed in these cells. Since conversion of the NH2-terminal residue from glycine to alanine should have little effect on the conformation of p60src, the inability of this mutant p60src protein to induce morphological transformation suggests that the myristoyl moiety is essential for the transforming activity of the protein.
authors.forename: M P
authors.initials: MP
authors.lastname: Kamps
authors.forename: J E
authors.initials: JE
authors.lastname: Buss
authors.forename: B M
authors.initials: BM
authors.lastname: Sefton
mesh_terms: D000818:Animals; D001358:Avian Sarcoma Viruses / Q000201:enzymology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D005998:Glycine; D009154:Mutation; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src); D011494:Protein Kinases / Q000235:genetics*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D009227:Myristic Acids; D014764:Viral Proteins; D019814:Myristic Acid; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D005998:Glycine