The objective of this proposal is to begin to understand the molecular mechanism of action of mammalian cell surface receptors. As a model system, these studies will focus on the nerve growth factor (NGF) receptor which mediates the action of NGF upon neuronal cell growth and metabolism. These actions include promotion of survival, differentiation, neurite outgrowth and regulation of catecholamine biosynthesis of the peripheral nervous system. The long range goals in this study are to understand how these responses are built into a specific polypeptide hormone and its receptor, and what molecular signals are generated upon this interaction of NGF with its receptor. Using somatic cell genetics, recombinant DNA and gene transfer technology, the gene(s) encoding the NGF receptor will be isolated to (1) identify structurally important features of the receptor molecule and its gene; (2) study the molecular basis of differential receptor expression in neuronal cells both in culture and during development; and (3) correlate the presence of the NGF receptor with the various short and long-term effects of NGF. The characterization of the molecular and physiological properties of NGF receptor will advance our understanding of the structure, function, and regulation of growth factor receptors. Recent findings suggest that growth factor action may have implications in the development and expression of neoplastic transformation and may share common pathways in eliciting similar cellular responses. In addition, NGF and NGF receptor have been implicated in a number of inherited neurological disorders such as familial dysautonomia.
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