MAPK pathways transmit signals from the environment to the cellular machinery, eliciting responses that are specific for each stimulus. These pathways are essential for the survival of unicellular or complex eukaryotes. In higher eukaryotes, the improper regulation of MAPK pathways is at the core of some illnesses like inflammatory diseases or cancer.
MAPK pathways have been the subject of intense study for the last 15 years. The basic components of many of these pathways have been described and analysed in a large number of eukaryotes. However, little is known about how the MAPKKs are down regulated and the effects of this inactivation in the cell physiology. We will study the regulation of one of the key components of a MAPK pathway in the yeast Schizosacchar omyces pombe, the MAPKK Wis1. The MAPKK Wis1 is a key component of the Spc1 MAPK pathway in fission yeast.
The Spc1 pathway responds to high osmolarity, oxidative stress, heat shock, etc. In response to stress, Wis1 is activated by phosphorylation mediated by the MAPKKKs, Wis4 and Win1, and in turn, phosphorylates and activates the MAPK Spc1. We will try to understand how Wis1 is inactivated and how this inactivation is achieved, through the study of novel components of this pathway. The information obtained will be useful for the understanding of MAPK pathways in other eukaryotes and the development of specific drugs that target these pathways.
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