Human glioma PKC‐ι and PKC‐βII phosphorylate cyclin‐dependent kinase activating kinase during the cell cycle

Abstract.

Cell cycle phase transition is regulated in part by the trimeric enzyme, cyclin‐dependent kinase activating kinase (CAK) which phosphorylates and activates cyclin‐dependent kinases (cdks). Protein kinase C (PKC) inhibitors prevent cell cycle phase transition, suggesting a fundamental role for PKCs in cell cycle regulation. We report that in glioma cells, CAK (cdk7) is constitutively associated with PKC‐ι. In vitro phosphorylation, co‐immunoprecipitation, and analysis of phosphorylated proteins by autoradiography indicate that CAK (cdk7) is a substrate for PKC‐ι and PKC‐βII hyperphosphorylation. These results establish a role for PKC‐ι and PKC‐βII in the activation of CAK during the glioma cell cycle.