Detection of a novel quiescence-dependent protein kinase.
We have identified a cell quiescence-specific 33-kDa cytoplasmic protein kinase (p33(QIK), Quiescence-Induced Kinase) based on induction of p33(QIK)-specific kinase activity of cells growth-arrested in the quiescent phase and deactivation upon entry into the cell cycle. Blockage of macromolecular synthesis prevents p33(QIK) from deactivation, indicating a requirement of newly synthesized regulators for deactivation of p33(QIK) during G(0)/G(1) transition. Stress shock induces additional increases of p33(QIK) activity in a quiescence-dependent manner that correlates with induction of apoptosis. Using a specific antibody to Krs1/Mst2 protein, we found that p33(QIK) is related to p63(Krs1) and is distinguishable from a 36-kDa protein kinase, which is induced through proteolytic modification of activated p63(Krs1) in proliferating cells undergoing apoptosis. p33(QIK) is constantly expressed in quiescent, proliferating, and apoptotic quiescent cells. Regulation of p33(QIK) activity involves protein phosphorylation/dephosphorylation in a proteolysis-independent manner. Regulation of p33(QIK) and related p63(Krs1) and p36 appears to involve distinct pathways in quiescent and proliferating cells, respectively. Our results illustrate the relevance of p33(QIK) activity for cell quiescence that may provide a new insight into signaling pathways regulated in cells during quiescence and quiescence-related apoptosis.
Wang
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Department of Comparative Medicine, The University of Tennessee College of Veterinary Medicine, Knoxville 37996, USA. hcrwang@utk.edu
Fecteau
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KA
D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D003600:Cytosol / Q000201:enzymology; D047630:Depsipeptides; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D010456:Peptides, Cyclic; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011994:Recombinant Proteins / Q000378:metabolism; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction; D013312:Stress, Physiological; D000099317:Hippo Kinases
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053148:Caspase 3; D020169:Caspases; D047630:Depsipeptides; D010456:Peptides, Cyclic; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011994:Recombinant Proteins; D000090742:Serine-Threonine Kinase 3; C087123:romidepsin; C413217:quiescence-induced kinase; C097835:STK3 protein, human; D000099317:Hippo Kinases; C490818:Stk3 protein, mouse; C516868:PTPRU protein, human; C516869:Ptpru protein, mouse; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse