This project is aimed at determining the molecular interactions which are causally involved in regulating initiation of cell division. Our two primary objectives are to determine the site of action of insulin and epidermal growth factor and to define events which occur subsequent to thrombin binding to its receptor which are involved in initiation of cell division. We have previously shown that thrombin action at the cell surface is sufficient to initiate cell division and that this division requires thrombin occupancy of specific cell surface receptors. We propose to use similar techniques of immobilization and quantitation of released material to determine whether cell surface action of non-proteolytic peptide factors such as insulin and epdermal growth factor is also sufficient to generate a mitogenic signal. Several lines of evidence indicate that thrombin proteolytically cleaves its own receptor as a part of the mitogenic signal. Therefore, we are working toward understanding the mitogenic interaction between thrombin and its receptor (1) by isloating and characterizing the thrombin receptor, and (2) by preparing fluorescent derivatives of thrombin to visualize their binding to thrombin receptors and to determine if events such as receptor redistributions are necessary for thrombin to initiate cell division.
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