title: Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast.
abstract: In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms. The first one involves TORC2 and its downstream effector, Akt ortholog Gad8, which together with TORC1 target Psk1 increase protein levels of the PKC ortholog Pck2 during cell wall stress or glucose starvation. Also, Ryh1 activates Pmk1 in a TORC2-independent fashion by prompting plasma membrane trafficking and stabilization of upstream activators of the MAPK cascade, including PDK ortholog Ksg1 or Rho1 GEF Rgf1. Besides, stress-activated Pmk1 cross-inhibits Ryh1 signaling by decreasing the GTPase activation cycle, and this ensures cell growth during alterations in phosphoinositide metabolism. Our results reveal a highly intricate cross-regulatory relationship between both pathways that warrants adequate cell adaptation and survival in response to environmental changes.
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
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: Beatriz
authors.initials: B
authors.lastname: Vázquez-Marín
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: 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: 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: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Cansado
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000172:deficiency; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D012270:Ribosomes / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology* / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D010716:Phosphatidylinositols; D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose