title: Rho2 is a target of the farnesyltransferase Cpp1 and acts upstream of Pmk1 mitogen-activated protein kinase signaling in fission yeast.
abstract: We have previously demonstrated that knockout of the calcineurin gene or inhibition of calcineurin activity by immunosuppressants resulted in hypersensitivity to Cl- in fission yeast. We also demonstrated that knockout of the components of the Pmk1 mitogen-activated protein kinase (MAPK) pathway, such as Pmk1 or Pek1 complemented the hypersensitivity to Cl-. Using this interaction between calcineurin and Pmk1 MAPK, here we developed a genetic screen that aims to identify new regulators of the Pmk1 signaling and isolated vic (viable in the presence of immunosuppressant and chloride ion) mutants. One of the mutants, vic1-1, carried a missense mutation in the cpp1+ gene encoding a beta subunit of the protein farnesyltransferase, which caused an amino acid substitution of aspartate 155 of Cpp1 to asparagine (Cpp1(D155N)). Analysis of the mutant strain revealed that Rho2 is a novel target of Cpp1. Moreover, Cpp1 and Rho2 act upstream of Pck2-Pmk1 MAPK signaling pathway, thereby resulting in the vic phenotype upon their mutations. Interestingly, compared with other substrates of Cpp1, defects of Rho2 function were more phenotypically manifested by the Cpp1(D155N) mutation. Together, our results demonstrate that Cpp1 is a key component of the Pck2-Pmk1 signaling through the spatial control of the small GTPase Rho2.
authors.affiliation: Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kuno
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.forename: Yuta
authors.initials: Y
authors.lastname: Asayama
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
mesh_terms: D000483:Alleles; D002462:Cell Membrane / Q000378:metabolism; D051231:Farnesyltranstransferase / Q000378:metabolism*; D005800:Genes, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D021122:Protein Subunits / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; C092804:Rho2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C516337:Cpp1 protein, S pombe; D051231:Farnesyltranstransferase; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D020741:rho GTP-Binding Proteins