title: Multiple layers of regulation influence cell integrity control by the PKC ortholog Pck2 in fission yeast.
abstract: The fission yeast protein kinase C (PKC) ortholog Pck2 controls cell wall synthesis and is a major upstream activator of the cell integrity pathway (CIP) and its core component, the MAP kinase Pmk1 (also known as Spm1), in response to environmental stimuli. We show that in vivo phosphorylation of Pck2 at the conserved T842 activation loop during growth and in response to different stresses is mediated by the phosphoinositide-dependent kinase (PDK) ortholog Ksg1 and an autophosphorylation mechanism. However, T842 phosphorylation is not essential for Pmk1 activation, and putative phosphorylation at T846 might play an additional role in Pck2 catalytic activation and downstream signaling. These events, together with turn motif autophosphorylation at T984 and binding to small GTPases Rho1 and/or Rho2, stabilize Pck2 and render it competent to exert its biological functions. Remarkably, the target of rapamycin complex 2 (TORC2) does not participate in the catalytic activation of Pck2, but instead contributes to de novo Pck2 synthesis, which is essential to activate the CIP in response to cell wall damage or glucose exhaustion. These results unveil a novel mechanism whereby TOR regulates PKC function at a translational level, and they add a new regulatory layer to MAPK signaling cascades.
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain marisa@um.es jcansado@um.es.
authors.forename: Marisa
authors.initials: M
authors.lastname: Madrid
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Jiménez
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sánchez-Mir
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Soto
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Franco
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Jero
authors.initials: J
authors.lastname: Vicente-Soler
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Gacto
authors.affiliation: Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas/Departamento de Microbiología y Genética, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain marisa@um.es jcansado@um.es.
authors.forename: José
authors.initials: J
authors.lastname: Cansado
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C523461:Tor1 protein, S pombe; C118141:KSG1 protein, S pombe; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D020741:rho GTP-Binding Proteins; C511156:rho1 protein, S pombe; D005947:Glucose
keywords: Cell integrity; Ksg1; MAP kinase; Pck2; Pmk1; S. pombe; Tor1