The long term goal of this project is to understand the molecular mechanisms that keep oocytes arrested and how fertilization breaks this cell cycle arrest. One of the very earliest changes triggered by fertilization is the dramatic, transient and one-time activation of a 42 kDa cytoplasmic mitogen-activated protein kinase, p43MAPK, a key player in a wide range of mitogen-activation signal transduction cascades. In fertilized clam oocytes, this one-time activation of p42MAPK appears to be required for the release of oocytes from cell cycle arrest. With the recently developed cell free systems from quiescent oocytes that respond to oncogenic ras protein by reproducing the ras-dependent activation of p42MAPK in vitro, we will use a combination of biochemical and genetic approaches to answer the following questions. 1. What are the molecular mechanisms that couple fertilization and activation of ras to the transient, one-time activation of p42MAPK and the release of oocytes from cell cycle arrest? 2. What regulates the subsequent inactivation of p42MAP? 3. What is p80, a protein that shares a ser/thr/tyr kinase domain with p42MAPK, and what is its role in the events triggered by fertilization?
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