Zebrafish G protein 2 is required for VEGF signaling during angiogenesis


Vascular endothelial growth factor (VEGF) is a major mediator of pathologic angiogenesis, a process necessary for the formation of new blood vessels to support tumor growth. Historically, VEGF has been thought to signal via receptor tyrosine kinases, which are not typically considered to be G protein dependent. Here, we show that targeted knockdown of the G protein gng2 gene (G 2) blocks the normal angiogenic process in developing zebrafish embryos. Moreover, loss of gng2 function inhibits the ability of VEGF to promote the angiogenic sprouting of blood vessels by attenuating VEGF induced phosphorylation of phospholipase C-gamma1 (PLC 1) and serine/threonine kinase (AKT). Collectively, these results demonstrate a novel interaction between G 2and VEGF-dependent pathways to regulate the angiogenic process in a whole-animal model. Blocking VEGF function using a humanized anti-VEGF antibody has emerged as a promising treatment for colorectal, non–small lung cell, and breast cancers. However, this treatment may cause considerable side effects. Our findings provide a new opportunity for cotargeting G protein– and VEGFdependent pathways to synergistically block pathologic angiogenesis, which may lead to a safer and more efficacious therapeutic regimen to fight cancer. (Blood. 2006;108:160-166)

DOI: 10.1182/blood-2005-09-3706

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@inproceedings{Leung2006ZebrafishGP, title={Zebrafish G protein 2 is required for VEGF signaling during angiogenesis}, author={Tinchung Leung and Hui Hiong Chen and Anna Maria Stauffer and Kathryn E. Giger and Soniya Sinha and Eric James Horstick and Jasper E. Humbert and Carl A. Hansen and Janet D. Robishaw}, year={2006} }