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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Cycle Proteins*
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Enzyme Activation
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Enzyme Inhibitors / metabolism
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Fungal Proteins*
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MAP Kinase Kinase 1*
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Mitogen-Activated Protein Kinase Kinases
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Phosphorylases
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Schizosaccharomyces / enzymology*
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Schizosaccharomyces / genetics
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Schizosaccharomyces pombe Proteins
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Sequence Homology, Amino Acid
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Signal Transduction
Substances
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Cell Cycle Proteins
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Enzyme Inhibitors
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Fungal Proteins
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Schizosaccharomyces pombe Proteins
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Phosphorylases
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Protein Kinases
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Mek1 protein, S pombe
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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Pmk1 protein, Magnaporthe grisea
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases