Modulators of MAPK pathway activity during filamentous growth in Saccharomyces cerevisiae .
| Autor: | Pujari AN; Department of Biological Sciences, University at Buffalo, Buffalo, New York 14260., Cullen PJ; Department of Biological Sciences, University at Buffalo, Buffalo, New York 14260. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 23. Date of Electronic Publication: 2023 Dec 23. |
| DOI: | 10.1101/2023.12.22.573138 |
| Abstrakt: | Mitogen-activated protein kinase (MAPK) pathways control the response to intrinsic and extrinsic stimuli. In the budding yeast Saccharomyces cerevisiae , cells undergo filamentous growth, which is regulated by the fMAPK pathway. To better understand the regulation of the fMAPK pathway, a genetic screen was performed to identify spontaneous mutants with elevated activity of an fMAPK-pathway dependent growth reporter ( ste4 FUS1-HIS3 ). In total, 159 mutants were isolated and analyzed by secondary screens for invasive growth by the plate-washing assay, and filament formation by microscopy. Thirty-two mutants were selected for whole-genome sequencing, which identified new alleles in genes encoding known regulators of the fMAPK pathway. These included gain-of-function alleles in STE11, which encodes the MAPKKK, as well as loss-of-function alleles in KSS1, which encodes the MAP kinase, and RGA1, which encodes a GTPase activating protein (GAP) for CDC42 . New alleles in previously identified pathway modulators were also uncovered in ALY1, AIM44, RCK2, IRA2, REG1 and in genes that regulate protein folding ( KAR2 ), glycosylation ( MNN4 ), and turnover ( BLM10 ). C-terminal truncations in the transcription factor Ste12p were also uncovered that resulted in elevated reporter activity, presumably identifying an inhibitory domain in the C-terminus of the protein. We also show that a wide variety of filamentous growth phenotypes result from mutations in different regulators of the response. The alleles identified here expand the connections surrounding MAPK pathway regulation and reveal new features of proteins that function in the signaling cascade. Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interests in the study. |
| Databáze: | MEDLINE |
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