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Turnover and bypass of p21-activated kinase during Cdc42-dependent MAPK signaling in yeast.
González, Beatriz; Mirzaei, Mahnoosh; Basu, Sukanya; Pujari, Atindra N; Vandermeulen, Matthew D; Prabhakar, Aditi; Cullen, Paul J.
Afiliación
  • González B; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
  • Mirzaei M; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
  • Basu S; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
  • Pujari AN; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
  • Vandermeulen MD; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
  • Prabhakar A; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
  • Cullen PJ; Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York, USA. Electronic address: pjcullen@buffalo.edu.
J Biol Chem ; 299(11): 105297, 2023 11.
Article en En | MEDLINE | ID: mdl-37774975
Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular behaviors, including the response to stress and cell differentiation, and are highly conserved across eukaryotes. MAPK pathways can be activated by the interaction between the small GTPase Cdc42p and the p21-activated kinase (Ste20p in yeast). By studying MAPK pathway regulation in yeast, we recently found that the active conformation of Cdc42p is regulated by turnover, which impacts the activity of the pathway that regulates filamentous growth (fMAPK). Here, we show that Ste20p is regulated in a similar manner and is turned over by the 26S proteasome. This turnover did not occur when Ste20p was bound to Cdc42p, which presumably stabilized the protein to sustain MAPK pathway signaling. Although Ste20p is a major component of the fMAPK pathway, genetic approaches here identified a Ste20p-independent branch of signaling. Ste20p-independent signaling partially required the fMAPK pathway scaffold and Cdc42p-interacting protein, Bem4p, while Ste20p-dependent signaling required the 14-3-3 proteins, Bmh1p and Bmh2p. Interestingly, Ste20p-independent signaling was inhibited by one of the GTPase-activating proteins for Cdc42p, Rga1p, which unexpectedly dampened basal but not active fMAPK pathway activity. These new regulatory features of the Rho GTPase and p21-activated kinase module may extend to related pathways in other systems.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Proteína de Unión al GTP cdc42 de Saccharomyces cerevisiae / Proteínas Quinasas Activadas por Mitógenos / Proteínas de Saccharomyces cerevisiae / Quinasas p21 Activadas Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Proteína de Unión al GTP cdc42 de Saccharomyces cerevisiae / Proteínas Quinasas Activadas por Mitógenos / Proteínas de Saccharomyces cerevisiae / Quinasas p21 Activadas Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos