title: The MAPK kinase Pek1 acts as a phosphorylation-dependent molecular switch.
abstract: The mitogen-activated protein kinase (MAPK) pathway is a highly conserved eukaryotic signalling cascade that converts extracellular signals into various outputs, such as cell growth and differentiation. MAPK is phosphorylated and activated by a specific MAPK kinase (MAPKK): MAPKK is therefore considered to be an activating regulator of MAPK. Pmk1 is a MAPK that regulates cell integrity and which, with calcineurin phosphatase, antagonizes chloride homeostasis in fission yeast. We have now identified Pek1, a MAPKK for Pmk1 MAPK. We show here that Pek1, in its unphosphorylated form, acts as a potent negative regulator of Pmk1 MAPK signalling. Mkh1, an upstream MAPKK kinase (MAPKKK), converts Pek1 from being an inhibitor to an activator. Our results indicate that Pek1 has a dual stimulatory and inhibitory function which depends on its phosphorylation state. This switch-like mechanism could contribute to the all-or-none physiological response mediated by the MAPK signalling pathway.
authors.affiliation: Department of Pharmacology, Kobe University School of Medicine, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Sugiura
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: S
authors.initials: S
authors.lastname: Dhut
authors.forename: H
authors.initials: H
authors.lastname: Shuntoh
authors.forename: T
authors.initials: T
authors.lastname: Kuno
mesh_terms: D000595:Amino Acid Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005656:Fungal Proteins; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D006005:Phosphorylases; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D006005:Phosphorylases; D011494:Protein Kinases; C119549:Mek1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C102726:Pmk1 protein, Magnaporthe grisea; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases