Regulation of the p58GTA cell division control-related protein kinase during phorbol 12-myristate 13-acetate-induced terminal differentiation of U937 cells.
We describe the regulation of expression, activity and subcellular localization of a cell cycle control-related kinase, p58GTA, during the withdrawal from the cell cycle of U937 human leukemic cells induced by phorbol esters. Our studies indicate that steady-state mRNA, protein levels, transcription and subcellular localization of this kinase are affected in distinctly different manners by phorbol esters (phorbol 12-myristate 13-acetate, PMA). Steady-state mRNA levels increase dramatically within 1 h of PMA treatment, while steady-state protein levels increase only slightly. However, within 24 h of PMA treatment both steady-state p58GTA mRNA and protein levels decrease markedly. Assays of p58GTA protein kinase activity show that, even though steady-state protein levels are relatively constant, protein kinase activity increases within 30 min of PMA treatment, and then peaks at 2 h and 12 h after PMA treatment. Once again, p58GTA protein kinase activity decreases by 48 h to levels similar to unstimulated cells. These results suggest that the expression of the p58GTA protein kinase gene and, quite possibly, its post-translational modification are affected by phorbol esters in a complex manner.
Kraft
A S
AS
Division of Hematology/Oncology, University of Alabama, Birmingham 35294.
Wang
S S
SS
Xiang
J
J
Pouncey
L
L
Kidd
V J
VJ
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases; D015870:Gene Expression; D006410:Hematopoiesis; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases; D013755:Tetradecanoylphorbol Acetate