Integration of Cell Cycle Signals by Swe1 Protein Kinase
Cell division in budding yeast depends on the formation of a filamentous collar containing septin proteins. This collar forms at the base of the bud, marking the place in the membrane between the mother cell and the emerging bud that constricts during cytokinesis, ultimately forming two cells when mitosis is complete. New evidence now indicates that protein complexes formed with septins are critical in coordinating morphogenesis with cell division and proper tracking of temporal progression through the cell cycle. Sakchaisri et al. show that yeast cells use the status of multiple phosphorylation sites on the protein kinase Swe1 to keep track of cell cycle progression and assembly of the necessary complexes organized at the bud neck. Genetic analysis and use of a designed form of protein kinase Cla4 sensitive to a specific inhibitor showed that the Cla4 protein contributes to phosphorylation of Swe1 during S phase of the cell cycle. Mutants with weakly functioning alleles of another protein kinase, Cdc5, lacked further phosphorylation of Swe1 that normally occurs right before entry into mitosis. Thus, accumulation of highly phosphorylated Swe1 provides the cell with an indicator that the cycle is progressing properly and that the necessary components are assembled in septin complexes. These phosphorylation events tag Swe1 for ubiquitin-dependent degradation, which in turn relieves Swe1's inhibitory phosphorylation of the critical cyclin-dependent kinase (Cdc28) that controls initiation of mitosis.
Cell cycle, division, integration, protein, kinase
Sakchaisri, K.; Asano, S.; Yu, L. R.; Shulewitz, J.; Park, C. J.; Park, J. E.; Cho, Y. W.; Veenstra, Timothy D.; Thorner, J.; and Lee, K. S., "Integration of Cell Cycle Signals by Swe1 Protein Kinase" (2004). Pharmaceutical Sciences Faculty Publications. 465.