title: Feedback regulation of MAPK signalling by an RNA-binding protein.
abstract: Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes that convert extracellular signals into various outputs such as cell growth, differentiation and cell death. MAPK phosphatases selectively inactivate MAPKs by dephosphorylating critical phosphothreonine and phosphotyrosine residues. The transcriptional induction of MAPK phosphatase expression by various stimuli, including MAPK activation, has been well documented as a negative-feedback mechanism of MAPK signalling. Here we show that Rnc1, a novel K-homology-type RNA-binding protein in fission yeast, binds and stabilizes Pmp1 messenger RNA, the MAPK phosphatase for Pmk1 (refs 10, 11). Rnc1 therefore acts as a negative regulator of Pmk1 signalling. Notably, Pmk1 phosphorylates Rnc1, causing enhancement of the RNA-binding activity of Rnc1. Thus, Rnc1 is a component of a new negative-feedback loop that regulates the Pmk1 pathway through its binding to Pmp1 mRNA. Our findings--the post-transcriptional mRNA stabilization of a MAPK phosphatase mediated by an RNA-binding protein--provide an additional regulatory mechanism for fine-tuning of MAPK signalling pathways.
authors.affiliation: Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. sugiurar@med.kobe-u.ac.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Hisato
authors.initials: H
authors.lastname: Shuntoh
authors.forename: Susie O
authors.initials: SO
authors.lastname: Sio
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kuno
mesh_terms: D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1; D025461:Feedback, Physiological; D005656:Fungal Proteins; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D012359:tRNA Methyltransferases
chemical_list: D005656:Fungal Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D012359:tRNA Methyltransferases; D020928:Mitogen-Activated Protein Kinases; C102726:Pmk1 protein, Magnaporthe grisea; D003851:Deoxyribonucleases; C077501:TRM2 protein, S cerevisiae; C110459:Pmp1 protein, S pombe; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases