Proenkephalin-processing enzymes in chromaffin granules: model for neuropeptide biosynthesis.
Our discovery of precursor preference of processing enzymes indicates possible development of future drugs that target specific proteases uniquely associated associated with processing of a particular prohormone. For example, selective processing of PE by the PTP suggests that future evaluation of modulation of PTP through central nervous system drug reagents may modify the endogenous analgesic effects of the enkephalins. With respect to blood pressure, neuropeptide Y (NPY) that is released from sympathetic nerve terminals is a strong vasoconstrictor. Our finding that only PTP (not PC1/3, PC2, or the aspartic proteinase) possesses the ability to convert pro-NPY to NPY suggests that investigation of inhibitors of peripheral PTP in blood pressure regulation should be initiated. Overall, elucidation of the proteolytic components required in prohormone processing will provide insights into the molecular mechanisms of human disease.
Hook
V Y
VY
Department of Medicine, University of California at San Diego, USCD Medical Center, California 92130-8227, USA.
Schiller
M R
MR
Azaryan
A V
AV
Tezapsidis
N
N
D000313:Adrenal Medulla / Q000201:enzymology; D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D002837:Chromaffin Granules / Q000201:enzymology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D045683:Furin; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000096:biosynthesis*; D009842:Oligopeptides / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013381:Subtilisins / Q000378:metabolism*
D004745:Enkephalins; D009479:Neuropeptides; D009842:Oligopeptides; D011498:Protein Precursors; D011994:Recombinant Proteins; C029992:proenkephalin; D013381:Subtilisins; D045683:Furin; D003546:Cysteine Endopeptidases; C083275:prohormone thiol protease; D016282:Aspartic Acid Endopeptidases