RT Journal Article T1 Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1 A1 Tatjer, Laura A1 Sacristán Reviriego, Almudena A1 Casado, Carlos A1 González, Asier A1 Rodríguez-Porrata, Boris A1 Palacios, Lorena A1 Canadell, David A1 Serra-Cardona, Albert A1 Martín Brieva, Humberto A1 Molina Martín, María A1 Joaquín Ariño, AB 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. PB Oxford University Press (OUP) SN 1943-2631 YR 2015 FD 2015-11-05 LK https://hdl.handle.net/20.500.14352/114583 UL https://hdl.handle.net/20.500.14352/114583 LA eng NO Tatjer, Laura, et al. «Wide-Ranging Effects of the Yeast Ptc1 Protein Phosphatase Acting Through the MAPK Kinase Mkk1». Genetics, vol. 202, n.o 1, enero de 2016, pp. 141-56. DOI.org (Crossref), https://doi.org/10.1534/genetics.115.183202. NO Ministerio de Ciencia e Innovación (España) NO Ministerio de Economía y Competitividad (España) NO Comunidad Autónoma de Madrid DS Docta Complutense RD 7 abr 2025