Role of MAPK and Protein Tyrosine Phosphatase Complexes in Signaling

University Of Colorado At Boulder, Boulder CO

Investigators

Abstract

Mitogen activated protein kinases (MAPKs) stimulate pathways consisting of sequentially acting protein kinases which regulate growth and development in eukaryotic organisms from yeast to mammals. A lot of work has been done on the activation of these pathways, but much less on the inactivation. This investigator is looking at the latter, by examining the protein phosphatases that inactivate them. She has previously found that two protein tyrosine phosphatases (PTPs), Ptp2 and Ptp3, inactivate stress activated MAPKs, Hog 1 and Mpk1 in yeast. In this research the function of higher order complexes, Hog1-Hog1, PTP-PTP and Hog1-Ptp2 in the high osmolarity glycerol (HOG) path will be examined since protein complexes are important in MAPK signaling. The subunit organization of these complexes will be determined, mutations disrupting these complexes will be introduced, and the ability of these mutants to signal will be examined. The signaling pathways that sense heat stress in eukaryotes are not well understood. Another objective of this project is to identify the mechanism by which heat stress activates Hog 1 and the role of PTPs in this process. The upstream regulators of the HOG pathway which are necessary for heat stress activation of Hog 1 will be characterized. Ptp2 and Ptp3 have a protective function, since strains lacking them are heat stress sensitive due to Hog 1 hyperactivation. Experiments outlined here will test whether PIPs are necessary for adaptation and if they prevent cross talk with the cell wall integrity pathway, which is activated by heat stress.