K252a inhibits the phosphorylation of pRb without changing the levels of G1 cyclins and Cdk2 protein in human hepatoma cells.
A protein kinase inhibitor K252a suppressed the growth of HuH7 hepatoma cells and the hyperphosphorylation of retinoblastoma protein (pRb) at late G1 phase of cell cycle. However, K252a treatment did not alter the levels of cyclin D1, cyclin E, cyclin A and Cdk2 protein bound to cyclin E or cyclin A. Therefore, the K252a inhibition of pRb phosphorylation is considered to be brought about probably by inhibiting the action of Cdk-cyclin complex rather than by changing its cellular level. These results also suggest that K252a is a useful tool for investigating the mechanism of phosphorylation of pRb mediated by Cdk-cyclin.
Nakayama
T
T
First Department of Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hashimoto
Y
Y
Kaneko
Y
Y
Kurokawa
K
K
D042846:CDC2-CDC28 Kinases; D002227:Carbazoles / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000302:isolation & purification / Q000378:metabolism*; D016213:Cyclins / Q000302:isolation & purification / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D026121:Indole Alkaloids; D007700:Kinetics; D008113:Liver Neoplasms; D015513:Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000302:isolation & purification / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002227:Carbazoles; D016213:Cyclins; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; C049985:staurosporine aglycone; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases