Cross-talk between ERK and p38-based MAPK pathways in the yeast S. cerevisiae.

PAULA DUNAYEVICH; RODRIGO BALTANÁS; ALEJANDRO COLMAN LERNER

Buenos Aires

Congreso; SAIB Annual Meeting Argentine Society for Biochemistry and Molecular Biology XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (BUENOS AIRES); 2013

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Understanding how cells integrate multiple simultaneous stimuli to decide their future behavior is a challenge. We study MAPK cascade pathways in the yeast S. cerevisiae: the ERK-based cascaded activated by mating pheromone (PR) and the p38-based one activated by high osmolarity (HOG). Recently, using single cell analysis, we found an unexpected cross-talk between them: in yeast adapted to high osmolarity, PR stimulates HOG (Baltanas et al 2013). It does so by ?creating? an osmotic imbalance functionally similar to an osmolarity shock: PR increases the efflux of glycerol (the osmolyte that yeast use to counteract a high external osmolarity), causing loss of turgor, leading to HOG activation. Now, we isolated a point mutant of the yeast p38 Hog1 that it is only activated by a bona-fide high osmolarity shock and not by pheromone. Our initial characterization suggests that the mutant p38 fails to translocate to the nucleus after pheromone treatment, indicating that the two inputs regulate differently the p38 retention in the cytoplasm, probably by modulating the expression or activity of anchoring proteins. Interestingly, two of the four mammalian p38s isoforms conserve in the equivalent position the same amino acid than Hog1, while the other two have an amino acid similar to that of our mutant, suggesting an important role of this position in the subfunctionalization of these kinases.