9319439 Hook Cell-cell communication in neuroendocrine systems utilizes small, potent, peptide hormones and neurotransmitters that are secreted from nerve cells. These peptide hormones and peptide neurotransmitters are synthesized as large protein precursors or prohormones that require specific proteolytic processing to yield the smaller physiologically active peptides. The prohormone processing enzymes represent an important point of regulation since it is this step where the inactive prohormone is converted to the smaller active forms. Active processing enzymes are prerequisite for the formation of potent functionally relevant neuropeptides. Dr. Hook i examining the role of a 70 kDa aspartyl protease in manufacturing enkephalin and neuropeptide Y peptides from its larger precursor products. These two peptides serve very important functions. Enkephalin is an endogenous opiate that plays a critical role in controlling pain and Neuropeptide Y is shown to be involved in feeding, shifting of biological rhythms, hypotension and reproduction. Dr. Hook will use state-of- the-art technologies to purify and characterize this enzyme. She will then generate large quantities of the prohormone to establish that the newly purified protease produces enkephalin and neuropeptide Y. Finally, Dr. Hook will use a technique called directed mutagenesis to determine the specific sites of action of the 70 kDa aspartyl protease. The results from this work is fundamental for understanding the molecular basis of precursor processing in generating active neuropeptides as well as contributing to a more general understanding about the control of biologically important messengers. The greatest promise of this basic research on how peptides are normally regulated may be in ultimate treatment of drug addiction since it appears that the regulation of the levels and activities of enkephalin may be involved. ***
