Activation of the protein kinase p38 in the spindle assembly checkpoint and mitotic arrest.
The mitogen-activated protein kinase (MAPK) superfamily comprises classical MAPK (also called ERK), c-Jun amino-terminal or stress-activated protein kinase (JNK or SAPK), and p38. Although MAPK is essential for meiotic processes in Xenopus oocytes and the spindle assembly checkpoint in Xenopus egg extracts, the role of members of the MAPK superfamily in M phase or the spindle assembly checkpoint during somatic cell cycles has not been elucidated. The kinase p38, but not MAPK or JNK, was activated in mammalian cultured cells when the cells were arrested in M phase by disruption of the spindle with nocodazole. Addition of activated recombinant p38 to Xenopus cell-free extracts caused arrest of the extracts in M phase, and injection of activated p38 into cleaving embryos induced mitotic arrest. Treatment of NIH 3T3 cells with a specific inhibitor of p38 suppressed activation of the checkpoint by nocodazole. Thus, p38 functions as a component of the spindle assembly checkpoint in somatic cell cycles.
Takenaka
K
K
Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-01, Japan.
Moriguchi
T
T
Nishida
E
E
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000378:metabolism / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; D016200:Maturation-Promoting Factor / Q000378:metabolism; D051379:Mice; D054639:Mitogen-Activated Protein Kinase Phosphatases; D020928:Mitogen-Activated Protein Kinases; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D016196:S Phase; D008941:Spindle Apparatus / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D017874:Immediate-Early Proteins; D011725:Pyridines; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016200:Maturation-Promoting Factor; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human; C482567:Map2k6 protein, mouse; C096688:DUSP1 protein, Xenopus; D054639:Mitogen-Activated Protein Kinase Phosphatases; D017027:Protein Tyrosine Phosphatases; C093642:SB 203580; D015739:Nocodazole