title: Activation of the cell integrity pathway is channelled through diverse signalling elements in fission yeast.
abstract: MAPK Pmk1p is the central element of a cascade involved in the maintenance of cell integrity and other functions in Schizosaccharomyces pombe. Pmk1p becomes activated by multiple stressing situations and also during cell separation. GTPase Rho2p acts upstream of the protein kinase C homolog Pck2p to activate the Pmk1 signalling pathway through direct interaction with MAPKKK Mkh1p. In this work we analyzed the functional significance of both Rho2p and Pck2p in the transduction of various stress signals by the cell integrity pathway. The results indicate that basal Pmk1p activity can be positively regulated by alternative mechanisms which are independent on the control by Rho2p and/or Pck2p. Unexpectedly, Pck1p, another protein kinase C homolog, negatively modulates Pmk1p basal activity by an unknown mechanism. Moreover, different elements appear to regulate the stress-induced activation of Pmk1p depending on the nature of the triggering stimuli. Whereas Pmk1p activation induced by hyper- or hypotonic stresses is channeled through Rho2p-Pck2p, other stressors, like glucose deprivation or cell wall disturbance, are transduced via other pathways in addition to that of Rho2p-Pck2p. On the contrary, Pmk1p activation observed during cell separation or after treatment with hydrogen peroxide does not involve Rho2p-Pck2p. Finally, Pck2p function is critical to maintain a Pmk1p basal activity that allows Pmk1p activation induced by heat stress. These data demonstrate the existence of a complex signalling network modulating Pmk1p activation in response to a variety of stresses in fission yeast.
authors.affiliation: Department of Genetics and Microbiology, Facultad de Biología, University of Murcia, 30071, Campus Universitario de Espinardo, Murcia, Spain.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Barba
authors.forename: Teresa
authors.initials: T
authors.lastname: Soto
authors.forename: Marisa
authors.initials: M
authors.lastname: Madrid
authors.forename: Andrés
authors.initials: A
authors.lastname: Núñez
authors.forename: Jeronima
authors.initials: J
authors.lastname: Vicente
authors.forename: Mariano
authors.initials: M
authors.lastname: Gacto
authors.forename: José
authors.initials: J
authors.lastname: Cansado
mesh_terms: D002453:Cell Cycle; D004789:Enzyme Activation; D005947:Glucose / Q000172:deficiency; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; C092804:Rho2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D006861:Hydrogen Peroxide; C511267:Pck1 protein, S pombe; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D020741:rho GTP-Binding Proteins; D005947:Glucose