title: Saccharomyces cerevisiae mid2p is a potential cell wall stress sensor and upstream activator of the PKC1-MPK1 cell integrity pathway.
abstract: The MID2 gene of Saccharomyces cerevisiae encodes a protein with structural features indicative of a plasma membrane-associated cell wall sensor. MID2 was isolated as a multicopy activator of the Skn7p transcription factor. Deletion of MID2 causes resistance to calcofluor white, diminished production of stress-induced cell wall chitin under a variety of conditions, and changes in growth rate and viability in a number of different cell wall biosynthesis mutants. Overexpression of MID2 causes hyperaccumulation of chitin and increased sensitivity to calcofluor white. alpha-Factor hypersensitivity of mid2Delta mutants can be suppressed by overexpression of upstream elements of the cell integrity pathway, including PKC1, RHO1, WSC1, and WSC2. Mid2p and Wsc1p appear to have overlapping roles in maintaining cell integrity since mid2Delta wsc1Delta mutants are inviable on medium that does not contain osmotic support. A role for MID2 in the cell integrity pathway is further supported by the finding that MID2 is required for induction of Mpk1p tyrosine phosphorylation during exposure to alpha-factor, calcofluor white, or high temperature. Our data are consistent with a role for Mid2p in sensing cell wall stress and in activation of a response that includes both increased chitin synthesis and the Mpk1p mitogen-activated protein kinase cell integrity pathway. In addition, we have identified an open reading frame, MTL1, which encodes a protein with both structural and functional similarity to Mid2p.
authors.affiliation: Department of Biology, McGill University, Montreal, Quebec, Canada H3A 1B1.
authors.forename: T
authors.initials: T
authors.lastname: Ketela
authors.forename: R
authors.initials: R
authors.lastname: Green
authors.forename: H
authors.initials: H
authors.lastname: Bussey
mesh_terms: D001557:Benzenesulfonates / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D002473:Cell Wall / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002686:Chitin / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004790:Enzyme Induction; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D016153:Genes, Suppressor / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D000072235:Mating Factor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001557:Benzenesulfonates; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C091625:MID2 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C083962:SKN7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D002686:Chitin; D019000:Phosphotyrosine; D000072235:Mating Factor; C007061:C.I. Fluorescent Brightening Agent 28; D011494:Protein Kinases; C097993:Pkc1 protein, Trichoderma reesei; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae