title: Rga4 modulates the activity of the fission yeast cell integrity MAPK pathway by acting as a Rho2 GTPase-activating protein.
abstract: Rho GTPase-activating proteins (GAPs) are responsible for the inactivation of Rho GTPases, which are involved in the regulation of critical biological responses in eukaryotic cells, ranging from cell cycle control to cellular morphogenesis. The genome of fission yeast Schizosaccharomyces pombe contains six genes coding for putative Rho GTPases, whereas nine genes code for predicted Rho GAPs (Rga1 to Rga9). One of them, Rga4, has been recently described as a Cdc42 GAP, involved in the control of cell diameter and symmetry in fission yeast. In this work we show that Rga4 is also a Rho2 GAP that negatively modulates the activity of the cell integrity pathway and its main effector, MAPK Pmk1. The DYRK-type protein kinase Pom1, which regulates both the localization and phosphorylation state of Rga4, is also a negative regulator of the Pmk1 pathway, but this control is not dependent upon the Rga4 role as a Rho2-GAP. Hence, two subsets of Rga4 negatively regulate Cdc42 and Rho2 functions in a specific and unrelated way. Finally, we show that Rga7, another Rho2 GAP, down-regulates the Pmk1 pathway in addition to Rga4. These results reinforce the notion of the existence of complex mechanisms determining the selectivity of Rho GAPs toward Rho GTPases and their functions.
authors.affiliation: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Soto
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Villar-Tajadura
authors.forename: Marisa
authors.initials: M
authors.lastname: Madrid
authors.forename: Jero
authors.initials: J
authors.lastname: Vicente
authors.forename: Mariano
authors.initials: M
authors.lastname: Gacto
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez
authors.forename: José
authors.initials: J
authors.lastname: Cansado
mesh_terms: D015536:Down-Regulation; D000939:Epitopes / Q000737:chemistry; D005656:Fungal Proteins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D012568:Schizosaccharomyces / Q000201:enzymology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000939:Epitopes; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; C529495:Rga4 protein, S pombe; C092804:Rho2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D020558:GTP Phosphohydrolases; D020741:rho GTP-Binding Proteins