The splice variants of vascular endothelial growth factor (VEGF) and their receptors.
AffiliationThe Cancer Research Campaign Department of Drug Development and the CRC and University of Manchester Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, M20 4BX, UK.
MetadataShow full item record
AbstractVascular endothelial growth factor (VEGF) is a secreted mitogen highly specific for cultured endothelial cells. In vivo VEGF induces microvascular permeability and plays a central role in both angiogenesis and vasculogenesis. VEGF is a promising target for therapeutic intervention in certain pathological conditions that are angiogenesis dependent, most notably the neovascularisation of growing tumours. Through alternative mRNA splicing, a single gene gives rise to several distinct isoforms of VEGF, which differ in their expression patterns as well as their biochemical and biological properties. Two VEGF receptor tyrosine kinases (VEGFRs) have been identified, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 seems to mediate almost all observed endothelial cell responses to VEGF, whereas roles for VEGFR-1 are more elusive. VEGFR-1 might act predominantly as a ligand-binding molecule, sequestering VEGF from VEGFR-2 signalling. Several isoform-specific VEGF receptors exist that modulate VEGF activity. Neuropilin-1 acts as a co-receptor for VEGF(165), enhancing its binding to VEGFR-2 and its bioactivity. Heparan sulphate proteoglycans (HSPGs), as well as binding certain VEGF isoforms, interact with both VEGFR-1 and VEGFR-2. HSPGs have a wide variety of functions, such as the ability to partially restore lost function to damaged VEGF(165) and thereby prolonging its biological activity.
CitationThe splice variants of vascular endothelial growth factor (VEGF) and their receptors. 2001, 114 (Pt 5):853-65 J. Cell. Sci.
JournalJournal of Cell Science
- Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia.
- Authors: Ozaki NK, Beharry KD, Nishihara KC, Akmal Y, Ang JG, Sheikh R, Modanlou HD
- Issue date: 2002 May
- A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases.
- Authors: Meyer M, Clauss M, Lepple-Wienhues A, Waltenberger J, Augustin HG, Ziche M, Lanz C, Büttner M, Rziha HJ, Dehio C
- Issue date: 1999 Jan 15
- Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system.
- Authors: Kremer C, Breier G, Risau W, Plate KH
- Issue date: 1997 Sep 1
- Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant.
- Authors: Whittle C, Gillespie K, Harrison R, Mathieson PW, Harper SJ
- Issue date: 1999 Sep
- Vascular endothelial growth factor (VEGF) and its receptors.
- Authors: Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z
- Issue date: 1999 Jan