Human glioma PKC-iota and PKC-betaII phosphorylate cyclin-dependent kinase activating kinase during the cell cycle.
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-iota. In vitro phosphorylation, co-immunoprecipitation, and analysis of phosphorylated proteins by autoradiography indicate that CAK (cdk7) is a substrate for PKC-iota and PKC-betaII hyperphosphorylation. These results establish a role for PKC-iota and PKC-betaII in the activation of CAK during the glioma cell cycle.
Acevedo-Duncan
M
M
James A. Haley Veterans Hospital, Tampa, FL 33612, USA. macevedo@chuma.cas.usf.edu
Patel
R
R
Whelan
S
S
Bicaku
E
E
D002453:Cell Cycle / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D064546:Protein Kinase C beta; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000099293:Protein Kinase C-lambda
D018844:Cyclin-Dependent Kinases; D007527:Isoenzymes; D009281:Naphthalenes; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D017346:Protein Serine-Threonine Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase; D000099293:Protein Kinase C-lambda; C061465:calphostin complex; C000722416:CDK7 protein, human