Cbk1 kinase and Bck2 control MAP kinase activation and inactivation during heat shock
| Autor: | Francis C. Luca, Venkata K. Kuravi, Manasi Puri, Cornelia Kurischko |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Gene Expression Regulation Enzymologic MAP2K7 03 medical and health sciences Gene Expression Regulation Fungal Heat shock protein ASK1 Phosphorylation Heat shock Molecular Biology 030304 developmental biology 0303 health sciences biology MAP kinase kinase kinase 030302 biochemistry & molecular biology Cyclin-dependent kinase 2 Intracellular Signaling Peptides and Proteins Articles Cell Biology Signaling Cell biology Enzyme Activation biology.protein Dual-Specificity Phosphatases Mitogen-Activated Protein Kinases Cyclin-dependent kinase 7 Heat-Shock Response |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e11-04-0371 |
| Popis: | Cbk1 kinase was previously implicated in regulating polarized morphogenesis, gene expression, and cell integrity. This study reveals that Cbk1 regulates heat shock signaling and stress adaptation by modulating Mpk1 activity and MAPK phosphatase localization. A model for Cbk1 and its putative substrate for these functions is presented. Saccharomyces cerevisiae Cbk1 kinase is a LATS/NDR tumor suppressor orthologue and component of the Regulation of Ace2 and Morphogenesis signaling network. Cbk1 was previously implicated in regulating polarized morphogenesis, gene expression, and cell integrity. Here we establish that Cbk1 is critical for heat shock and cell wall stress signaling via Bck2, a protein associated with the Pkc1-Mpk1 cell integrity pathway. We demonstrate that cbk1 and bck2 loss-of-function mutations prevent Mpk1 kinase activation and Mpk1-dependent gene expression but do not disrupt Mpk1 Thr-190/Tyr-192 phosphorylation. Bck2 overexpression partially restores Mpk1-dependent Rlm1 transcription factor activity in cbk1 mutants, suggesting that Bck2 functions downstream of Cbk1. We demonstrate that Bck2 precisely colocalizes with the mitogen-activated protein kinase (MAPK) phosphatase Sdp1. During heat shock, Bck2 and Sdp1 transiently redistribute from nuclei and the cytosol to mitochondria and other cytoplasmic puncta before returning to their pre-stressed localization patterns. Significantly, Cbk1 inhibition delays the return of Bck2 and Sdp1 to their pre-stressed localization patterns and delays Mpk1 Thr-190/Tyr-192 dephosphorylation upon heat shock adaptation. We conclude that Cbk1 and Bck2 are required for Mpk1 activation during heat shock and cell wall stress and for Mpk1 dephosphorylation during heat shock adaptation. These data provide the first evidence that Cbk1 kinase regulates MAPK-dependent stress signaling and provide mechanistic insight into Sdp1 phosphatase regulation. |
| Databáze: | OpenAIRE |
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