| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 27, 25022-25029, July 6, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Medicine, University of California, and
Department of Veterans Affairs Medical Center, San Diego, California
92161 and the Chromogranin A (CgA), the major
soluble protein in catecholamine storage vesicles, serves as a
prohormone that is cleaved into bioactive peptides that inhibit
catecholamine release, providing an autocrine, negative feedback
mechanism for regulating catecholamine responses during stress.
However, the proteases responsible for the processing of CgA and
release of bioactive peptides have not been established. Recently, we
found that chromaffin cells express components of the plasmin(ogen)
system, including tissue plasminogen activator, which is targeted to
catecholamine storage vesicles and released with CgA and catecholamines
in response to sympathoadrenal stimulation, and high affinity cell
surface receptors for plasminogen, to promote plasminogen activation at
the cell surface. In the present study, we investigated processing of
CgA by plasmin and sought to identify specific bioactive CgA peptides
produced by plasmin proteolysis. Highly purified human CgA (hCgA) was
produced by expression in Escherichia coli and purification
using metal affinity chromatography. hCgA was digested with plasmin.
Matrix-assisted laser desorption/ionization mass spectrometry
identified a major peptide produced with a mass/charge ratio
(m/z) of 1546, corresponding uniquely to
hCgA-(360-373), the identity of which was confirmed by reverse
phase high pressure liquid chromatography and amino-terminal microsequencing. hCgA-(360-373) was selectively liberated by plasmin from hCgA at early time points and was stable even after prolonged exposure to plasmin. The corresponding synthetic peptide markedly inhibited nicotine-induced catecholamine release from pheochromocytoma cells. These results identify plasmin as a protease, present in the
local environment of the chromaffin cell, that selectively cleaves CgA
to generate a bioactive fragment, hCgA-(360-373), that inhibits
nicotinic-mediated catecholamine release. These results suggest that
the plasminogen/plasmin system through its interaction with CgA may
play a major role in catecholaminergic function and suggest a specific
mechanism as well as a discrete CgA peptide through which this effect
is mediated.
Proteolytic Cleavage of Chromogranin A (CgA) by Plasmin
SELECTIVE LIBERATION OF A SPECIFIC BIOACTIVE CgA FRAGMENT THAT
REGULATES CATECHOLAMINE RELEASE*
, and Department of Vascular Biology, The Scripps
Research Institute, La Jolla, California 92037
*
This work was supported by National Institutes of Health
Grants HL-50398, HL-58120, HL-38272, HL-07261, and DK-07671 and by the
Department of Veterans Affairs.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. R. Mahapatra Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure Cardiovasc Res, December 1, 2008; 80(3): 330 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Biswas, S. M. Vaingankar, M. Mahata, M. Das, J. R. Gayen, L. Taupenot, J. W. Torpey, D. T. O'Connor, and S. K. Mahata Proteolytic Cleavage of Human Chromogranin A Containing Naturally Occurring Catestatin Variants: Differential Processing at Catestatin Region by Plasmin Endocrinology, February 1, 2008; 149(2): 749 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-R. Hwang, C. Garza, C. Mosier, T. Toneff, E. Wunderlich, P. Goldsmith, and V. Hook Cathepsin L Expression Is Directed to Secretory Vesicles for Enkephalin Neuropeptide Biosynthesis and Secretion J. Biol. Chem., March 30, 2007; 282(13): 9556 - 9563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Miles, N. M. Andronicos, N. Baik, and R. J. Parmer Cell-Surface Actin Binds Plasminogen and Modulates Neurotransmitter Release from Catecholaminergic Cells J. Neurosci., December 13, 2006; 26(50): 13017 - 13024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Taupenot, K. L. Harper, and D. T. O'Connor The Chromogranin-Secretogranin Family N. Engl. J. Med., March 20, 2003; 348(12): 1134 - 1149. [Full Text] [PDF]
|
|
|
|
|
|
B. Colombo, R. Longhi, C. Marinzi, F. Magni, A. Cattaneo, S. H. Yoo, F. Curnis, and A. Corti Cleavage of Chromogranin A N-terminal Domain by Plasmin Provides a New Mechanism for Regulating Cell Adhesion J. Biol. Chem., November 22, 2002; 277(48): 45911 - 45919. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
