Thiol-based direct threat sensing by the stress-activated protein kinase Hog1
| Autor: | Daniel Finley, Helena M. Schnell, Steven P. Gygi, Joao A. Paulo, Yagmur Micoogullari, Miguel A. Prado, John Hanna, Angel Guerra-Moreno, Jessie Ang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
MAPK/ERK pathway
Saccharomyces cerevisiae Proteins Arsenate Reductases Osmotic shock MAP Kinase Signaling System Chemistry Kinase Endoplasmic reticulum Saccharomyces cerevisiae Cell Biology Biochemistry Article Arsenic Cell biology Basic-Leucine Zipper Transcription Factors ARR3 Phosphorylation Mitogen-Activated Protein Kinases Protein kinase A Molecular Biology Transcription factor |
| Zdroj: | Sci Signal |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.aaw4956 |
| Popis: | The yeast stress-activated protein kinase Hog1 is best known for its role in mediating the response to osmotic stress, but it is also activated by various mechanistically distinct environmental stressors, including heat shock, endoplasmic reticulum stress, and arsenic. In the osmotic stress response, the signal is sensed upstream and relayed to Hog1 through a kinase cascade. Here, we identified a mode of Hog1 function whereby Hog1 senses arsenic through a direct physical interaction that requires three conserved cysteine residues located adjacent to the catalytic loop. These residues were essential for Hog1-mediated protection against arsenic, were dispensable for the response to osmotic stress, and promoted the nuclear localization of Hog1 upon exposure of cells to arsenic. Hog1 promoted arsenic detoxification by stimulating phosphorylation of the transcription factor Yap8, promoting Yap8 nuclear localization, and stimulating the transcription of the only known Yap8 targets, ARR2 and ARR3, both of which encode proteins that promote arsenic efflux. The related human kinases ERK1 and ERK2 also bound to arsenic in vitro, suggesting that this may be a conserved feature of some members of the mitogen-activated protein kinase (MAPK) family. These data provide a mechanistic basis for understanding how stress-activated kinases can sense distinct threats and perform highly specific adaptive responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|