Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\18266961
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2008 ; 12
(3
): 781-95
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
gamma-Secretase: a multifaceted regulator of angiogenesis
#MMPMID18266961
Boulton ME
; Cai J
; Grant MB
J Cell Mol Med
2008[Jun]; 12
(3
): 781-95
PMID18266961
show ga
Physiological angiogenesis is essential for development, homeostasis and tissue
repair but pathological neovascularization is a major feature of tumours,
rheumatoid arthritis and ocular complications. Studies over the last decade have
identified gamma-secretase, a presenilin-dependent protease, as a key regulator
of angiogenesis through: (i) regulated intramembrane proteolysis and
transmembrane cleavage of receptors (e.g. VEGFR-1, Notch, ErbB-4, IGFI-R)
followed by translocation of the intracellular domain to the nucleus, (ii)
translocation of full length membrane-bound receptors to the nucleus (VEGFR-1),
(iii) phosphorylation of membrane bound proteins (VEGFR-1 and ErbB-4), (iv)
modulation of adherens junctions (cadherin) and regulation of permeability and
(v) cleavage of amyloid precursor protein to amyloid-? which is able to regulate
the angiogenic process. The gamma-secretase-induced translocation of receptors to
the nucleus provides an alternative intracellular signalling pathway, which acts
as a potent regulator of transcription. gamma-secretase is a complex composed of
four different integral proteins (presenilin, nicastrin, Aph-1 and Pen-2), which
determine the stability, substrate binding, substrate specificity and proteolytic
activity of gamma-secretase. This seeming complexity allows numerous
possibilities for the development of targeted gamma-secretase
agonists/antagonists, which can specifically regulate the angiogenic process.
This review will consider the structure and function of gamma-secretase, the
growing evidence for its role in angiogenesis and the substrates involved,
gamma-secretase as a therapeutic target and future challenges in this area.
|Amyloid Precursor Protein Secretases/chemistry/*metabolism
[MESH]
|Amyloid beta-Protein Precursor/metabolism
[MESH]
|Cadherins/metabolism
[MESH]
|Cell Membrane/enzymology/metabolism
[MESH]
|Endopeptidases
[MESH]
|ErbB Receptors/metabolism
[MESH]
|Membrane Proteins/metabolism
[MESH]
|Models, Biological
[MESH]
|Neovascularization, Pathologic/*prevention & control
[MESH]
free
free
free
