Processing of chromaffin granule proteins: a profusion of proteases?
Evidence suggests that proenkephalin and members of the chromogranin/secretogranin family of proteins are prohormone precursors, giving rise to a variety of peptides with biologic activity. However, the specific proteases responsible for cleaving these proteins in vivo have not been fully established. Several candidate proteases have been described, some of which have been shown to cleave these proteins in vitro. Proteolytic processing of the chromogranins may be particularly complex, occurring in specific tissue-dependent patterns. To account for this level of complexity several protease systems may be operative, either alone or in concert, both within the neurosecretory granule and in the extracellular space. Specific proteases which are available within neurosecretory cells or in the local extracellular environment, and which may cleave these prohormones include PC1 and PC2 (recently described members of the Kex2/furin family of endoproteases), as well as kallikrein, acetylcholinesterase, and, more recently, the plasminogen/plasmin protease system. The potential role of these specific proteases in the processing of proenkephalin and the chromogranins is discussed, in particular, in the context of possible processing clues available from recent analysis of cDNA and genomic intron/exon structure.
Parmer
R J
RJ
Department of Medicine, University of California, San Diego 92161.
Miles
L A
LA
Xi
X P
XP
Gill
B M
BM
Wu
H J
HJ
O'Connor
D T
DT
D000818:Animals; D002837:Chromaffin Granules / Q000378:metabolism*; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005091:Exons; D006801:Humans; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D002864:Chromogranins; D004745:Enkephalins; D011498:Protein Precursors; D011506:Proteins; C029992:proenkephalin; D010450:Endopeptidases