title: Phosphatases driving mitosis: pushing the gas and lifting the brakes.
abstract: Entry into and progression through mitosis depends critically on the establishment and maintenance of protein phosphorylation. For this reason, studies on mitotic progression have focused heavily on the activation of MPF (M phase promoting factor), a cyclin-dependent kinase responsible for phosphorylating proteins that execute the dynamic events of mitosis. Recent work, however, has significantly expanded our understanding of mechanisms that allow accumulation of phosphoproteins at M phase, suggesting that mitotic entry relies not only on MPF activation but also on the inhibition of antimitotic phosphatases. It is now clear that there exists a separate, albeit equally important, signaling pathway for the inactivation of protein phosphatases at the G2/M transition. This pathway, which is governed by the kinase Greatwall is essential for both entry into and maintenance of M phase. This chapter will outline the molecular events regulating entry into mitosis, specifically highlighting the role that protein phosphorylation plays in triggering both MPF activation and the inhibition of phosphatase activity that would otherwise prevent accumulation of mitotic phosphoproteins. These intricate regulatory pathways are essential for maintaining normal cell division and preventing inappropriate cell proliferation, a central hallmark of cancer cells.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Schoolof Medicine, Durham, North Carolina, USA.
authors.forename: Erika Segear
authors.initials: ES
authors.lastname: Johnson
authors.forename: Sally
authors.initials: S
authors.lastname: Kornbluth
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016200:Maturation-Promoting Factor / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D029867:Xenopus Proteins / Q000502:physiology; D014982:Xenopus laevis; D020687:cdc25 Phosphatases / Q000502:physiology; D020666:ras-GRF1 / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010750:Phosphoproteins; D020033:Protein Isoforms; D029867:Xenopus Proteins; C064321:cyclic AMP-regulated phosphoprotein 19; C075663:endosulfine; D020666:ras-GRF1; C490167:Gwl protein, Drosophila; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D016200:Maturation-Promoting Factor; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases