title: Inhibitor-2 induced M-phase arrest in Xenopus cycling egg extracts is dependent on MAPK activation.
abstract: The evolutionarily-conserved protein phosphatase 1 (PP1) plays a central role in dephosphorylation of phosphoproteins during the M phase of the cell cycle. We demonstrate here that the PP1 inhibitor inhibitor-2 protein (Inh-2) induces an M-phase arrest in Xenopus cycling egg extracts. Interestingly, the characteristics of this M-phase arrest are similar to those of mitogen-activated protein kinase (p42MAPK)-induced M-phase arrest. This prompted us to investigate whether Inh-2-induced M-phase arrest was dependent on activation of the p42MAPK pathway. We demonstrate here that MAPK activity is required for Inh-2-induced M-phase arrest, as inhibition of MAPK by PD98059 allowed cycling extracts to exit M phase, despite the presence of Inh-2. We next investigated whether Inh-2 phosphorylation by the MAPK pathway was required to induce an M-phase arrest. We discovered that while p90Rsk (a MAPK protein required for M-phase arrest) is able to phosphorylate Inh-2, this phosphorylation is not required for Inh-2 function. Overall, our results suggest a novel mechanism linking p42MAPK and PP1 pathways during M phase of the cell cycle.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7 arian.khandani@sickkids.ca.
authors.forename: Arian
authors.initials: A
authors.lastname: Khandani
authors.forename: Mahmood
authors.initials: M
authors.lastname: Mohtashami
authors.forename: Anne
authors.initials: A
authors.lastname: Camirand
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002457:Cell Extracts / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010957:Plasmids; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D014169:Transformation, Bacterial; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*; D000097847:Protein Phosphatase Inhibitory Proteins
chemical_list: D018797:Cell Cycle Proteins; D002457:Cell Extracts; D005419:Flavonoids; D019950:Mitogen-Activated Protein Kinase 1; D054645:Protein Phosphatase 1; D011506:Proteins; D011994:Recombinant Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D029867:Xenopus Proteins; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one