Gamma-secretase regulates VEGFR-1 signalling in vascular endothelium and RPE

Michael E Boulton; Jun Cai; Maria B Grant; Yadan Zhang

doi:10.1007/978-0-387-74904-4_36

Gamma-secretase regulates VEGFR-1 signalling in vascular endothelium and RPE

Adv Exp Med Biol. 2008:613:313-9. doi: 10.1007/978-0-387-74904-4_36.

Authors

Michael E Boulton¹, Jun Cai, Maria B Grant, Yadan Zhang

Affiliation

¹ Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas 77550, USA. [email protected]

PMID: 18188959
DOI: 10.1007/978-0-387-74904-4_36

Abstract

In conclusion, gamma-secretase is expressed in both retinal microvascular endothelial cells and RPE cells and is able to elicit regulated intramembrane proteolysis of VEGFR1. Furthermore, gamma-secretase regulates the translocation of the intracellular domain of VEGFR1 as well as full length VEGFR1 in both cell types. Gamma-secretase is clearly able to act as a potent negative regulators of VEGFR2 induced in vitro angiogenesis but its role in the RPE has yet to be elucidated. We conclude that gamma-secretase may offer a therapeutic target for the treatment of both retinal and choroidal neovascularization.

Publication types

Review

MeSH terms

Amyloid Precursor Protein Secretases / genetics
Amyloid Precursor Protein Secretases / metabolism*
Animals
Capillary Permeability / physiology
Endothelium, Vascular / metabolism*
Gene Expression Regulation, Enzymologic*
Humans
Hydrolysis
Ligands
Neovascularization, Pathologic / pathology
Pigment Epithelium of Eye / metabolism*
Protein Isoforms / chemistry
Protein Isoforms / metabolism
Protein Structure, Tertiary
Signal Transduction*
Vascular Endothelial Growth Factor Receptor-1 / chemistry
Vascular Endothelial Growth Factor Receptor-1 / metabolism*

Substances

Ligands
Protein Isoforms
Vascular Endothelial Growth Factor Receptor-1
Amyloid Precursor Protein Secretases