Molecular Dissection of the Checkpoint Kinase Hsl1p
| Autor: | Elaine S.G. Bardes, Lee Szkotnicki, David A. Orlando, Daniel J. Lew, Kindra M. King, John Crutchley, Mignon A. Keaton, Trevin R. Zyla |
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| Rok vydání: | 2009 |
| Předmět: |
Protein-Arginine N-Methyltransferases
Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae Protein Serine-Threonine Kinases Biology Mitogen-activated protein kinase kinase Septin MAP2K7 Structure-Activity Relationship ASK1 Phosphorylation Molecular Biology Phylogeny Sequence Deletion Cyclin-dependent kinase 1 Cyclin-dependent kinase 2 Articles Cell Biology Protein Structure Tertiary Cell biology Enzyme Activation Protein Transport Wee1 biology.protein Cyclin-dependent kinase 7 Protein Kinases Protein Binding |
| Zdroj: | Molecular Biology of the Cell. 20:1926-1936 |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Cell shape can influence cell behavior. In Saccharomyces cerevisiae, bud emergence can influence cell cycle progression via the morphogenesis checkpoint. This surveillance pathway ensures that mitosis always follows bud formation by linking degradation of the mitosis-inhibitory kinase Swe1p (Wee1) to successful bud emergence. A crucial component of this pathway is the checkpoint kinase Hsl1p, which is activated upon bud emergence and promotes Swe1p degradation. We have dissected the large nonkinase domain of Hsl1p by using evolutionary conservation as a guide, identifying regions important for Hsl1p localization, function, and regulation. An autoinhibitory motif restrains Hsl1p activity when it is not properly localized to the mother-bud neck. Hsl1p lacking this motif is active as a kinase regardless of the assembly state of cytoskeletal septin filaments. However, the active but delocalized Hsl1p cannot promote Swe1p down-regulation, indicating that localization is required for Hsl1p function as well as Hsl1p activation. We also show that the septin-mediated Hsl1p regulation via the novel motif operates in parallel to a previously identified Hsl1p activation pathway involving phosphorylation of the Hsl1p kinase domain. We suggest that Hsl1p responds to alterations in septin organization, which themselves occur in response to the local geometry of the cell cortex. |
| Databáze: | OpenAIRE |
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