title: Possible integration of upstream signals at Cdc42 in filamentous differentiation of S. cerevisiae.
abstract: Various environmental stimuli (such as nitrogen starvation, short-chain alcohols and slowed DNA synthesis) induce filamentous differentiation in S. cerevisiae. Genetic mutations (such as deletion of the mitotic cyclin gene CLB2) cause constitutive filamentous differentiation. Although different stimulus-induced filamentous differentiation involves different signalling pathways, Cdc42 has been identified as a common regulator. We show here that Cdc42 is also required for hydroxyurea (HU)-induced and clb2Delta-caused filamentous growth. We show that the mitotic CDK Clb2/Cdc28 functions upstream of Cdc42 in regulating filamentous differentiation. This result points to possible existence of a Cdc42-MAPK-Clb2/Cdc28 positive feedback loop in the signalling of filamentous differentiation. We report isolation of a cdc42-Y40F allele that blocks HU-induced, but not nitrogen starvation-induced, short-chain alcohol-induced or clb2Delta-caused, filamentation. Based on these results, we propose a model in which Cdc42 functions as a possible integrator for the upstream signals of filamentous differentiation (from the filamentous growth MAPK pathway, the cAMP pathway and the Mec1/Rad53 checkpoint pathway). We also show evidence that the mitotic CDK inhibitor Swe1 may mediate the cross-talk between the cAMP and MAPK pathways.
authors.affiliation: Department of Medical Biochemistry and Genetics, Texas A&M University System, Health Science Center, 428 Reynolds Medical Building, College Station, TX 77843-1114, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.forename: Yi Wei
authors.initials: YW
authors.lastname: Jiang
mesh_terms: D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006918:Hydroxyurea / Q000378:metabolism / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D009584:Nitrogen; D006918:Hydroxyurea