Regulation of G2/M progression by the STE mitogen-activated protein kinase pathway in budding yeast filamentous growth.
Inoculation of diploid budding yeast onto nitrogen-poor agar media stimulates a MAPK pathway to promote filamentous growth. Characteristics of filamentous cells include a specific pattern of gene expression, elongated cell shape, polar budding pattern, persistent attachment to the mother cell, and a distinct cell cycle characterized by cell size control at G2/M. Although a requirement for MAPK signaling in filamentous gene expression is well established, the role of this pathway in the regulation of morphogenesis and the cell cycle remains obscure. We find that ectopic activation of the MAPK signal pathway induces a cell cycle shift to G2/M coordinately with other changes characteristic of filamentous growth. These effects are abrogated by overexpression of the yeast mitotic cyclins Clb1 and Clb2. In turn, yeast deficient for Clb2 or carrying cdc28-1N, an allele of CDK defective for mitotic functions, display enhanced filamentous differentiation and supersensitivity to the MAPK signal. Importantly, activation of Swe1-mediated inhibitory phosphorylation of Thr-18 and/or Tyr-19 of Cdc28 is not required for the MAPK pathway to affect the G2/M delay. Mutants expressing a nonphosphorylatable mutant Cdc28 or deficient for Swe1 exhibit low-nitrogen-dependent filamentous growth and are further induced by an ectopic MAPK signal. We infer that the MAPK pathway promotes filamentous growth by a novel mechanism that inhibits mitotic cyclin/CDK complexes and thereby modulates cell shape, budding pattern, and cell-cell connections.
Ahn
S H
SH
Center for Molecular Oncology and Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.
Acurio
A
A
Kron
S J
SJ
D002453:Cell Cycle / Q000235:genetics*; D048429:Cell Size / Q000235:genetics; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics; D016195:G2 Phase; D015966:Gene Expression Regulation, Fungal; D020930:MAP Kinase Kinase Kinases / Q000235:genetics*; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation; D012098:Reproduction; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors
D016213:Cyclins; D005656:Fungal Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C071596:ste11 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C067018:Ste11 protein, S cerevisiae