The ability to rapidly purify large quantities of endothelial cell growth factor (ECGF), the principal polypeptide mitogen for human endothelial cells, has led to the elucidation of the structure of the mitogen, the cloning of the gene which encodes the polypeptide, the identification of heparin as a modulator of ECGF mitogenic and chemotactic function, the design of radioreceptor and immunological assays for ECGF and the identification of an endothelial cell plasma membrane polypeptide as the receptor for ECGF and the appreciation that ECGF signal transduction is probably mediated by down-regulation of the ECGF receptor. In addition, investigator-intiated collaborative efforts have resulted in the definition of a new family of endothelial cell polypeptide mitogens to which ECGF is a member. We propose to expand these observations and further define the biochemical identify for this new polypeptide growth factor family by the elucidation of the structure for the ECGF receptor. We also propose a series of preliminary experiments which ask whether the ECGF receptor possesses the biochemical properties of an enzyme and/or substrate in order to provide a direction for future biochemical studies concerned with the mechanism of signal transduction for the ECGF receptor which are too ambitious for this proposal. We anticipate that the elucidation of the structure for the ECGF receptor polypeptide will advance our understanding of the role of the endothelial cell as a contributor to the maintenance of vascular homeostasis in vivo and may provide additional mechanistic insights for the prevention of vascular thrombosis in vivo.
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