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Mol Biol Cell ; 9(2): 451-67, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9450967

ABSTRACT

We have added constitutively active MAP kinase/ERK kinase (MEK), an activator of the mitogen-activated protein kinase (MAPK) signaling pathway, to cycling Xenopus egg extracts at various times during the cell cycle. p42MAPK activation during entry into M-phase arrested the cell cycle in metaphase, as has been shown previously. Unexpectedly, p42MAPK activation during interphase inhibited entry into M-phase. In these interphase-arrested extracts, H1 kinase activity remained low, Cdc2 was tyrosine phosphorylated, and nuclei continued to enlarge. The interphase arrest was overcome by recombinant cyclin B. In other experiments, p42MAPK activation by MEK or by Mos inhibited Cdc2 activation by cyclin B. PD098059, a specific inhibitor of MEK, blocked the effects of MEK(QP) and Mos. Mos-induced activation of p42MAPK did not inhibit DNA replication. These results indicate that, in addition to the established role of p42MAPK activation in M-phase arrest, the inappropriate activation of p42MAPK during interphase prevents normal entry into M-phase.


Subject(s)
CDC2 Protein Kinase/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase Kinases , Mitosis/physiology , Signal Transduction/physiology , Amino Acid Sequence , Animals , Cell Cycle/physiology , Cell Extracts , Cyclin B/biosynthesis , Cyclin B/pharmacology , Cyclin B/physiology , Cycloheximide/pharmacology , Enzyme Activation , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , MAP Kinase Kinase 1 , Molecular Sequence Data , Ovum , Phosphorylation , Protamine Kinase/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/pharmacology , Protein Serine-Threonine Kinases/physiology , Protein Synthesis Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/pharmacology , Protein-Tyrosine Kinases/physiology , Proto-Oncogene Proteins c-mos/pharmacology , Tyrosine/metabolism , Xenopus
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