Phosphorylation of middle T by pp60c-src: a switch for binding of phosphatidylinositol 3-kinase and optimal tumorigenesis.

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作者：

DA Talmage，R Freund，AT Young，J Dahl，CJ Dawe，TL Benjamin

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摘要：

Substitution of phenylalanine for tyrosine 315 of the polyoma virus middle T (mT) protein lowers the incidence and limits the spectrum of tumors induced following inoculation of the virus into newborn mice. This substitution removes the major site of phosphorylation by pp60 c- src without altering the ability of mT to associate with or to activate pp60 c- src. The mutant mT fails to show binding of a phosphatidylinositol 3-kinase (PtdIns 3-kinase) activity that is normally present in wild-type mT complexes. Furthermore, an anti-peptide antiserum that specifically recognizes mT lacking phosphate at tyrosine 315 precipitates binary (mT-pp60 c- src) but not ternary (mT-pp60 c- src-PtdIns 3-kinase) complexes from wild-type infected cell extracts. Reprecipitation with either anti-pp60 c- src or anti-mT serum brings down ternary complexes containing mT phosphorylated on tyrosine 315. Phosphorylation of mT by pp60 c- src in vivo is therefore a critical event for binding of PtdIns 3-kinase and for expression of the full tumorigenic potential of the virus.

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关键词：

Animals Mice, Inbred C3H Mice Tumor Virus Infections Cell Transformation, Neoplastic Cell Transformation, Viral Vanadates Tyrosine Phosphotransferases Oncogene Protein pp60(v-src