Contents
Guest Editor: Rebecca A. Lew
The
Zinc Metallopeptidase Family: New Faces, New Functions Pp 407-414
The
Intracellular Distribution and Secretion of Endopeptidases 24.15 (Ec 3.4.24.15)
and 24.16 (Ec 3.4.24.16) Pp
415-421
Emer S. Ferro, Flavia
R. Carreno, Camila Goni, Paula A.G. Garrido,Alessander O. Guimaraes, Leandro M.
Castro, Vitor Oliveira, Mauricio C. Araujo,Vanessa Rioli, Marcelo D. Gomes,
Jose Domingues Fontenele-Neto and Stephen Hyslop
Secretase-Mediated
Cell Surface Shedding of the Angiotensin-Converting Enzyme Pp
423-432
Edward T. Parkin,
Anthony J. Turner and Nigel M. Hooper
Hemodynamic
Regulation of Metallopeptidases within the Vasculature Pp
433-442
Philip M. Cummins,
Eoin J. Cotter and Paul A. Cahill
Metalloproteinase-Mediated
Shedding of Heparin-Binding Egf-Like Growth Factor and Its Pathophysiological Pp 443-450
Roles Shigeki
Higashiyama
Dine (Damage-Induced Neuronal
Endopeptidase) Pp 451-460
Sumiko Kiryu-Seo and
Hiroshi Kiyama
Endothelin
Converting Enzyme-2: A Processing Enzyme Involved in the Generation of Novel
Neuropeptides Pp 461-469
Hui Pan, Nino Mzhavia
and Lakshmi A. Devi
The
Role of Neuropeptide Processing Enzymes in Endocrine (Prostate) Cancer: EC
3.4.24.15 (EP24.15) Pp
471-478
Todd A. Swanson,
Sandra I. Kim, Michael Myers, Amanda Pabon, Keith D. Philibert,Mina Wang and
Marc J. Glucksman
Neprilysin 2: A Novel Messenger
Peptide-Inactivating Metalloprotease Pp 479-489
Tanja Ouimetn
Membrane Bound Members of the M1
Family: More Than Aminopeptidases Pp 491-500
Anthony L. Albiston,
Siying Ye and Siew Yeen Chai
Nardilysin,
A Basic Residues Specific Metallopeptidase That Mediates Cell Migration and
Proliferation Pp 501-508
Veronique Hospital and Annik
Prat
Abstracts
[Back
to top] The Zinc Metallopeptidase Family: New Faces, New Functions
Rebecca A. Lew
The abstract
for this article is not available.
[Back
to top] The Intracellular Distribution and Secretion of Endopeptidases
24.15 (Ec 3.4.24.15) and 24.16 (Ec 3.4.24.16)
Emer S. Ferro, Flavia R. Carreno, Camila Goni, Paula A.G. Garrido,Alessander O. Guimaraes, Leandro M. Castro, Vitor Oliveira, Mauricio C. Araujo,Vanessa Rioli, Marcelo D. Gomes, Jose Domingues Fontenele-Neto and Stephen Hyslop
Endopeptidase 24.15 (EC 3.4.24.15; EP24.15)
and endopeptidase 24.16 (EC 3.4.24.16; EP24.16) are enzymes involved in general
peptide metabolism in mammalian cells and tissues. This review will focus on
morphological and biochemical aspects related to the subcellular distribution
and secretion of these homologous enzymes in the central nervous system. These
are important issues for a better understanding of the functions of EP24.15 and
EP24.16 within neuroendocrine systems.
[Back
to top] Secretase-Mediated Cell Surface Shedding of the
Angiotensin-Converting Enzyme
Edward T. Parkin,
Anthony J. Turner and Nigel M. Hooper
Angiotensin-converting enzyme (ACE) is an
example of a membrane-bound protein, which is shed from the cell surface in a
soluble form by a post-translational proteolytic cleavage event involving a
secretase. The secretase cleavage site in somatic ACE has been mapped to
Arg-1203/Ser-1204, 24 residues proximal to the membrane-anchoring domain and
the ADAM (‘ a d isintegrin and metalloprotease’)
family of proteins may be involved in ACE shedding.
[Back
to top] Hemodynamic Regulation of Metallopeptidases within the
Vasculature
Philip M. Cummins,
Eoin J. Cotter and Paul A. Cahill
Hemodynamic forces associated with blood flow
play a vital role in the endothelial regulation of vascular tone, remodeling
and the initiation and progression of vascular diseases such as atherosclerosis
and hypertension. Crucial elements in endothelium-mediated events within the
blood vessel are bioactive peptide signals and their associated hydrolytic
enzymes. This review examines the relationship between hemodynamic forces such
as shear stress and cyclic strain, and an important group of peptide-degrading
enzymes within the endothelium, the thermolysin-like zinc metallopeptidases.
[Back to top] Metalloproteinase-Mediated
Shedding of Heparin-Binding Egf-Like Growth Factor and Its Pathophysiological
Roles Shigeki
Higashiyama
Heparin-binding EGF-like growth factor
(HB-EGF) exists as a membrane-anchored form (proHBEGF) and as its soluble cleaved
product (sHB-EGF). The conversion (ectodomain shedding) of proHB-EGF to sHB-EGF
is tightly regulated by specific metalloproteinases. Ectodomain shedding plays
a central role in GPCR-mediated EGFR transactivation. Antagonizing
metalloproteinases can inhibit EGFR transactivation and might be of therapeutic
value, for example in cardiac hypertrophy, skin remodeling and tumor growth.
[Back to top]
Dine
(Damage-Induced Neuronal Endopeptidase)
Sumiko Kiryu-Seo and
Hiroshi Kiyama
A unique central nervous system
(CNS)-specific metalloprotease, DINE/ECEL1 (damage induced neuronal
endopeptidase/ endothelin converting enzyme-like 1), has recently been added to
the M13/neprilysin (NEP) family. This enzyme was identified by two groups
independently using different approaches. In this review, we introduce the
characteristics of DINE/ECEL1 and focus on the mechanism underlying the
transcriptional regulation of DINE in response to neuronal injury.
[Back
to top] Endothelin Converting Enzyme-2: A Processing Enzyme Involved in
the Generation of Novel Neuropeptides
Members of several metalloprotease families
have been proposed to be involved in non-classical processing of neuroendocrine
precursors. Among them, endothelin converting enzyme-2 (ECE-2) is a good
candidate since it exhibits a neuroendocrine distribution, intracellular subcellular
localization, and an acidic pH optimum. The enzyme is able to generate a number
of biologically active peptides from peptide intermediates, suggesting an
important role for this enzyme in the biosynthesis of regulatory peptides.
These results are consistent with an important role for ECE-2 in the processing
of regulatory peptides at non-classical sites.
[Back
to top] The Role of Neuropeptide Processing Enzymes in Endocrine (Prostate)
Cancer: EC 3.4.24.15 (EP24.15)
Todd A. Swanson,
Sandra I. Kim, Michael Myers, Amanda Pabon, Keith D. Philibert,Mina Wang and
Marc J. Glucksman
The zinc metalloendopeptidase EC3.4.24.15
[EP24.15, thimet oligopeptidase], a neuropeptide processing enzyme, is central
to the formation and degradation of many bioactive peptides in the neural
proteome, and is highly expressed in normal prostate. EP24.15 actions are
increased in androgen-dependent prostate cancer compared to
androgen-independent; augmented by androgen treatment, and inhibited by
clinical GnRH analogs. The “neural” prostate includes: neuropeptides, cognate
receptors and processing enzymes regulating signaling of peptide-mediated
neural inputs.
[Back to top]
Neprilysin
2: A Novel Messenger Peptide-Inactivating Metalloprotease
Tanja Ouimetn
Neprilysin 2 is a
recently identified glycoprotein displaying the highest degree of sequence
identity with neprilysin (EC 3.4.24.11), the prototypical member of the M13
family of zinc-dependent metalloproteases. Whereas neprilysin has been shown to
be involved in the inactivation of endogenous messenger peptides, like
enkephalins and tachykinins, the true physiological functions of neprilysin 2
remain unknown.
[Back to top]
Membrane
Bound Members of the M1 Family: More Than Aminopeptidases
Anthony L. Albiston,
Siying Ye and Siew Yeen Chai
In mammals the M1 aminopeptidase family
consists of nine different proteins, five of which are integral membrane
proteins. The aminopeptidases are defined by two motifs in the catalytic
domain; a zinc binding motif HEXXH-(X18)-E and an exopeptidase motif
GXMEN. Aminopeptidases of this family are able to cleave a broad range of
peptides down to only to a single peptide. This ability to either generate or
degrade active peptide hormones is the focus of this review. In addition to
their capacity to degrade a range of peptides a number of these aminopeptidases
have novel functions that impact on cell signalling and will be discussed.
[Back
to top] Nardilysin, A Basic Residues Specific Metallopeptidase That
Mediates Cell Migration and Proliferation
Nardilysin (NRDc), a metallopeptidase of the
M16 family, presents, in vitro, cleavage specificity for basic residues.
Depending on the cell type, it is cytoplasmic, exported or cell surface
associated. As a new receptor for heparin-binding EGF-like growth factor
(HB-EGF), NRDc was recently shown to be involved in cellular migration and
proliferation. Since for those processes its enzymatic activity is not
required, it is now evident that nardilysin fulfills at least two distinct
functions, i.e. an HB-EGF modulator and a peptidase.