Structural and functional modification of pp60c-src associated with polyoma middle tumor antigen from infected or transformed cells.
The polyoma middle tumor antigen (MTAg) associates with the src proto-oncogene product pp60c-src in infected or transformed rodent cells. The tyrosine protein kinase activity of pp60c-src, as measured by in vitro phosphorylation of pp60c-src itself or the exogenous substrate enolase, was increased 10- to 20-fold in cells transformed or infected with transformation-competent polyoma virus compared with controls. pp60c-src associated with MTAg and precipitated with polyoma antitumor serum had a novel site(s) of in vitro tyrosine phosphorylation within its amino-terminal domain. These observations suggest that association of MTAg with pp60c-src alters the accessibility of pp60c-src tyrosine residues for phosphorylation in vitro and increases pp60c-src protein kinase activity. Several transformation-defective mutants of MTAg did not cause amino-terminal tyrosine phosphorylation of pp60c-src in vitro or enhance its protein kinase activity, suggesting that these properties correlate with the transforming ability of MTAg. However, one transformation-defective MTAg mutant, dl1015, did cause amino-terminal tyrosine phosphorylation of pp60c-src in vitro and did enhance its protein kinase activity. This suggests that properties of MTAg, in addition to modifying the structure and function of pp60c-src, may be important for transformation.
D000595:Amino Acid Sequence; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D051379:Mice; D010446:Peptide Fragments / Q000032:analysis; D010766:Phosphorylation; D019000:Phosphotyrosine; D011120:Polyomavirus / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src); D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000957:Antigens, Viral, Tumor; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)