Phosphatidylinositol turnover and transformation of cells by Abelson murine leukaemia virus.
The transforming protein of the Abelson murine leukaemia virus encodes a protein-tyrosine kinase. Previously, we have shown that in Abelson-transformed cells, the Abelson kinase regulates the phosphoserine content of ribosomal protein S6. Phorbol 12-myristate 13-acetate (TPA), which activates protein kinase C, induces the phosphorylation of S6 at the same five phosphopeptides as found in S6 isolated from Abelson-transformed cells. We have investigated three models whereby the Abelson kinase might regulate S6 phosphorylation via the activation of protein kinase C. First, the Abelson kinase could phosphorylate protein kinase C on tyrosine. However, we do not detect significant amounts of phosphotyrosine in protein kinase C in vivo. Second, it has been suggested that protein-tyrosine kinases might phosphorylate phosphatidylinositol. This could increase the intracellular levels of diacylglycerol and thereby activate protein kinase C. Our data strongly suggest that direct phosphorylation of phosphatidylinositol by the Abelson protein-tyrosine kinase has no physiological role. Third, an indirect activation of protein kinase C may occur via an increase in the rate of phosphoinositide breakdown. We have found that phosphoinositide breakdown appears to be constitutively activated in Abelson-transformed cells. The implications of these observations are discussed with regard to S6 phosphorylation and the mechanism of Abelson-induced transformation.
D000011:Abelson murine leukemia virus / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005796:Genes; D005814:Genes, Viral; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010716:Phosphatidylinositols / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases