Overactivation of the protein kinase C-signaling pathway suppresses the defects of cells lacking the Rho3/Rho4-GAP Rgd1p in Saccharomyces cerevisiae.
The nonessential RGD1 gene encodes a Rho-GTPase activating protein for the Rho3 and Rho4 proteins in Saccharomyces cerevisiae. Previous studies have revealed genetic interactions between RGD1 and the SLG1 and MID2 genes, encoding two putative sensors for cell integrity signaling, and VRP1 encoding an actin and myosin interacting protein involved in polarized growth. To better understand the role of Rgd1p, we isolated multicopy suppressor genes of the cell lethality of the double mutant rgd1Delta mid2Delta. RHO1 and RHO2 encoding two small GTPases, MKK1 encoding one of the MAP-kinase kinases in the protein kinase C (PKC) pathway, and MTL1, a MID2-homolog, were shown to suppress the rgd1Delta defects strengthening the functional links between RGD1 and the cell integrity pathway. Study of the transcriptional activity of Rlm1p, which is under the control of Mpk1p, the last kinase of the PKC pathway, and follow-up of the PST1 transcription, which is positively regulated by Rlm1p, indicate that the lack of RGD1 function diminishes the PKC pathway activity. We hypothesize that the rgd1Delta inactivation, at least through the hyperactivation of the small GTPases Rho3p and Rho4p, alters the secretory pathway and/or the actin cytoskeleton and decreases activity of the PKC pathway.
de Bettignies
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Laboratoire de Biologie Moléculaire et de Séquençage, UMR CNRS 5095, Bordeaux Cedex, France.
Thoraval
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Morel
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Peypouquet
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MF
Crouzet
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D000199:Actins / Q000378:metabolism; D015152:Blotting, Northern; D004247:DNA / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins; D009154:Mutation; D009218:Myosins / Q000378:metabolism; D010641:Phenotype; D010675:Pheromones / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015398:Signal Transduction; D013489:Suppression, Genetic; D013997:Time Factors; D014158:Transcription, Genetic; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology
D000199:Actins; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D010675:Pheromones; C449479:RGD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D009218:Myosins; C074647:RHO3 protein, S cerevisiae; C074648:RHO4 protein, S cerevisiae; D020741:rho GTP-Binding Proteins