Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation.
pp60c-src is phosphorylated in vivo at tyrosine 527, a residue not present in pp60v-src (its transforming homolog), and not at tyrosine 416, its site of in vitro autophosphorylation. To test the hypothesis that tyrosine phosphorylation  regulates pp60c-src biological activity, we constructed and studied pp60c-src mutants in which Tyr 527 and Tyr 416 were separately or coordinately altered to phenylalanine. Tyr----Phe 527 mutation strongly activated pp60c-src transforming and kinase activities, whereas the additional introduction of a Tyr----Phe 416 mutation suppressed these activities. Tyr----Phe 416 mutation of normal pp60c-src eliminated its partial transforming activity, which suggests that transient or otherwise restricted phosphorylation of Tyr 416 is important for pp60c-src function even though stable phosphorylation is not observed in vivo.
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005809:Genes, Regulator; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D015688:Oncogene Protein pp60(v-src); D010449:Peptide Mapping; D010766:Phosphorylation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012191:Retroviridae Proteins / Q000235:genetics*; D013489:Suppression, Genetic
D012191:Retroviridae Proteins; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)