title: Comparison of the effects of carboxyl terminal truncation and point mutations on pp60c-src activities.
abstract: pp60c-src kinase and transforming activities are negatively regulated by phosphorylation of Tyr 527, a residue 6 amino acids from its carboxyl terminus. Tyr 527 to Phe mutation has been shown to activate pp60c-src, yet pp60c-src(F527) is still less active than pp60v-src. To see if additional carboxyl terminal mutation can stimulate pp60c-src transforming activity to pp60v-src levels, we compared the properties of pp60c-src(Am517), a pp60c-src mutant in which the 17 carboxyl terminal amino acids were deleted, with those of pp60c-src(F527) and pp60c-src(F519), a protein in which the Tyr nearest to Tyr 527 was changed to Phe. Tyr 519 to Phe mutation did not affect pp60c-src activities while the Am517 mutation activated focus formation, growth in soft agarose, in vivo tumorigenicity and in vitro specific kinase activity to levels between those of pp60c-src and pp60c-src(F527). This contrasts with a previous study [Cartwright et al. (1987) Cell 49, 83-91] which reported that Am517 mutation enhances biological activities without enhanced kinase activity. These data support the hypotheses that (1) complete transformation by pp60c-src requires activation of its protein tyrosine kinase activity and (2) that downregulation by the pp60c-src carboxyl terminus is governed by phosphorylation of Tyr 527; additional changes beyond that needed to prevent this phosphorylation do not further enhance activity.
authors: Department of Molecular and Cell Biology, Pennsylvania State University, University Park 16802.
authors: P
authors: P
authors: Yaciuk
authors: M T
authors: MT
authors: Cannella
authors: D
authors: D
authors: Shalloway
mesh_terms: D000818:Animals; D002460:Cell Line; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016392:Proto-Oncogene Proteins pp60(c-src); D013379:Substrate Specificity
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)