title: Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1.
abstract: The Saccharomyces cerevisiae type 2C protein phosphatase Ptc1 is required for a wide variety of cellular functions, although only a few cellular targets have been identified. A genetic screen in search of mutations in protein kinase-encoding genes able to suppress multiple phenotypic traits caused by the ptc1 deletion yielded a single gene, MKK1, coding for a MAPK kinase (MAPKK) known to activate the cell-wall integrity (CWI) Slt2 MAPK. In contrast, mutation of the MKK1 paralog, MKK2, had a less significant effect. Deletion of MKK1 abolished the increased phosphorylation of Slt2 induced by the absence of Ptc1 both under basal and CWI pathway stimulatory conditions. We demonstrate that Ptc1 acts at the level of the MAPKKs of the CWI pathway, but only the Mkk1 kinase activity is essential for ptc1 mutants to display high Slt2 activation. We also show that Ptc1 is able to dephosphorylate Mkk1 in vitro. Our results reveal the preeminent role of Mkk1 in signaling through the CWI pathway and strongly suggest that hyperactivation of Slt2 caused by upregulation of Mkk1 is at the basis of most of the phenotypic defects associated with lack of Ptc1 function.
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Tatjer
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), 28040 Madrid, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Sacristán-Reviriego
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Casado
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: González
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: Boris
authors.initials: B
authors.lastname: Rodríguez-Porrata
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), 28040 Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Palacios
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Canadell
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Serra-Cardona
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), 28040 Madrid, Spain.
authors.forename: Humberto
authors.initials: H
authors.lastname: Martín
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), 28040 Madrid, Spain Joaquin.Arino@uab.es molmifa@ucm.es.
authors.forename: María
authors.identifier: http://orcid.org/0000-0003-0074-3309
authors.initials: M
authors.lastname: Molina
authors.affiliation: Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain Joaquin.Arino@uab.es molmifa@ucm.es.
authors.forename: Joaquín
authors.identifier: http://orcid.org/0000-0002-6774-2987
authors.initials: J
authors.lastname: Ariño
mesh_terms: D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; C000609667:MKK1 protein, S cerevisiae; C561307:MKK2 protein, S cerevisiae; D020929:Mitogen-Activated Protein Kinase Kinases; C087358:PTC1 protein, S cerevisiae; D054648:Protein Phosphatase 2
keywords: Saccharomyces cerevisiae; cell-wall integrity pathway; protein dephosphorylation; synthetic genetic interactions