Similarities and differences between the vascular endothelial growth factor (VEGF) splice variants

Neufeld, Gera; Cohen, Tzafra; Gitay-Goren, Hela; Poltorak, Zoya; Tessler, Shoshana; Sharon, R.; Gengrinovitch, Stela; Levi, Ben‐Zion

doi:10.1007/bf00437467

Cited by 138 publications

(85 citation statements)

References 46 publications

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“…VEGFR-1 and VEGFR-2 are high-affinity receptors for VEGF (Neufeld et al, 1996;Yancopoulos et al, 2000). Although VEGFR-1 and VEGFR-2 are structurally highly similar, their angiogenic signal transduction appears to differ drastically from each other.…”

Section: Discussionmentioning

confidence: 99%

“…VEGF activates a broad spectrum of biological responses in endothelial cells, including cell proliferation, migration, survival, differentiation and permeability to macromolecules (Waltenberger et al, 1994;Neufeld et al, 1996;Rahimi et al, 2000;Suarez and Ballmer-Hofer, 2001). Although VEGFR-1 and VEGFR-2 are structurally highly similar, their mechanisms of angiogenic signal transduction relay appear to differ drastically from each other.…”

Section: Introductionmentioning

confidence: 99%

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Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation

et al. 2004

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VEGFR-1 is devoid of ligand-dependent tyrosine autophosphorylation and its activation is not associated with proliferation of endothelial cells. The molecular mechanism responsible for this characteristic of VEGFR-1 is not known. In this study, we show that VEGFR-1 is devoid of ligand-dependent downregulation and failed to stimulate intracellular calcium release, cell migration and angiogenesis in vitro. To understand the molecular mechanisms responsible for the poor tyrosine autophosphorylation of VEGFR-1, we have either deleted the carboxyl terminus of VEGFR-1 or exchanged it with the carboxyl terminus of VEGFR-2. The deletion of carboxyl terminus of VEGFR-1 did not reverse its defective ligand-dependent autophosphorylation. The carboxyl terminus-swapped VEGFR-1, however, displayed ligand-dependent autophosphorylation, downregulation and also conveyed strong mitogenic responses. Thus, the carboxyl tail of VEGFR-1 restrains the ligand-dependent kinase activation and downregulation of VEGFR-1 and its ability to convey the angiogenic responses in endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation

et al. 2004

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“…There are five isoforms for VEGF-A resulting from alternative splicing of the same gene: VEGF 120 , VEGF 144 , VEGF 164 , VEGF 188 and VEGF 205 (Neufeld et al, 1996;Shima et al, 1996;Tober et al, 1998). Only the three most abundant isoforms, VEGF 120 , VEGF 164 , and VEGF 188 , were detected in the seven pools of RNA from non-TG ovaries and RNA from 20 human mutant TG ovaries, but the level of each was higher in TG ovaries than in non-TG ovaries ( Figure 6).…”

Section: Differential Enhancement Of Vegf-a But Not Vegf-b Levels Imentioning

confidence: 99%

Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2)

et al. 2004

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“…Differential splicing in exons 6 and 7 produces isoforms within each family with varying heparin binding activity (e.g. 189, 189b,165, 165b, etc) [14][15][16][17]. Since revascularisation and beta cell survival have been implicated in the short-and medium-term survival of islets, this study considers the role of the predominant pro-angiogenic, pro-epithelial survival isoform, VEGF 165 .…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor as a survival factor for human islets: effect of immunosuppressive drugs

et al. 2007

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Aims/hypothesis Rapamycin, part of the immunosuppressive regimen of the Edmonton protocol, has been shown to inhibit vascular endothelial growth factor (VEGF) production and VEGF-mediated survival signalling in tumour cell lines. This study investigates the survival-promoting activities of VEGF in human islets and the effects of rapamycin on islet viability.Materials and methods Levels of VEGF and its receptors in isolated human islets and whole pancreas was determined by western blotting and immunostaining. Islet viability following VEGF or immunosuppressive drug treatment was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Islet VEGF release was measured by ELISA. Mouse islets infected with an adenovirus expressing the gene for VEGF were transplanted syngeneically into streptozotocin-induced diabetic mice, with blood glucose levels measured three times per week. Results Isolated human islets produced multiple isoforms of VEGF and VEGF receptors 1, 2 and 3 and the coreceptor neuropilin 1. Exogenous VEGF (10 ng/ml) prevented human islet death induced by serum starvation, which suggests that VEGF can act as a survival factor for human islets. Transplantation of mouse islets infected with a VEGF-expressing adenovirus in a syngeneic model, improved glycaemic control at day 1 post-transplantation (p< 0.05). Rapamycin at 10 and 100 ng/ml significantly reduced islet VEGF release (by 37±4% and 43±6%, respectively; p<0.05) and at 100 ng/ml reduced islet viability (by 36±9%) and insulin release (by 47±7%, all vs vehicle-treated controls; p<0.05). Tacrolimus had no effect on islet VEGF release or viability. Conclusions/interpretation Our data suggest that rapamycin may have deleterious effects on islet survival posttransplantation, both through a direct effect on islet viability and indirectly through blockade of VEGF-mediated revascularisation.

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Similarities and differences between the vascular endothelial growth factor (VEGF) splice variants

Cited by 138 publications

References 46 publications

Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation

Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation

Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2)

Vascular endothelial growth factor as a survival factor for human islets: effect of immunosuppressive drugs

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