NDLI: Characterization of carboxypeptidase A6, an extracellular matrix peptidase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lyons, Peter J. Callaway, Myrasol B. Fricker, Lloyd D.
Description	Author Affiliation: Lyons PJ ( Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.)
Abstract	Carboxypeptidase A6 (CPA6) is a member of the M14 metallocarboxypeptidase family that is highly expressed in the adult mouse olfactory bulb and broadly expressed in embryonic brain and other tissues. A disruption in the human CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection. In this study the cellular distribution, processing, and substrate specificity of human CPA6 were investigated. The 50-kDa pro-CPA6 is routed through the constitutive secretory pathway, processed by furin or a furin-like enzyme into the 37-kDa active form, and secreted into the extracellular matrix. CPA6 cleaves the C-terminal residue from a range of substrates, including small synthetic substrates, larger peptides, and proteins. CPA6 has a preference for large hydrophobic C-terminal amino acids as well as histidine. Peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides were found to be processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. Whereas CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, CPA6 converts inactive angiotensin I into the biologically active angiotensin II. Taken together, these data suggest a role for CPA6 in the regulation of neuropeptides in the extracellular environment within the olfactory bulb and other parts of the brain.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	11
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-03-14
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carboxypeptidases A Chemistry Extracellular Matrix Enzymology Peptides Angiotensin I Animals Brain Metabolism Furin Histidine Mice Models, Biological Models, Molecular Neurotensin Olfactory Bulb Protein Structure, Tertiary Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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