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Blood, 1 July 2006, Vol. 108, No. 1, pp. 160-166. Prepublished online as a Blood First Edition Paper on March 14, 2006; DOI 10.1182/blood-2005-09-3706. This Article Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: 2005-09-3706v1 108/1/160    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leung, T. Articles by Robishaw, J. D Search for Related Content PubMed PubMed Citation Articles by Leung, T. Articles by Robishaw, J. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 22, 2005 Accepted February 17, 2006 Zebrafish G protein 2 is required for VEGF signaling during angiogenesis TinChung Leung*, Hui Chen, Anna M Stauffer, Kathryn E Giger, Soniya Sinha, Eric J Horstick, Jasper E Humbert, Carl A Hansen, and Janet D Robishaw Weis Center for Research, Geisinger Health System, Danville, PA, USA Department of Biological and Allied Health Sciences, Bloomsburg University, Bloomsburg, PA, USA * Corresponding author; email: tleung1{at}geisinger.edu. Vascular endothelial growth factor (VEGF) is a major mediator of pathological angiogenesis, a process necessary for the formation of new blood vessels to support tumor growth. Historically, VEGF is 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 (G2) 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 (PLC1) and serine/threonine kinase (AKT). Collectively, these results demonstrate a novel interaction between G2- and 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 co-targeting G protein- and VEGF-dependent pathways to synergistically block pathological angiogenesis, which may lead to a safer and more efficacious therapeutic regimen to fight cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Larhammar, K. Nordstrom, and T. A. Larsson Evolution of vertebrate rod and cone phototransduction genes Phil Trans R Soc B, October 12, 2009; 364(1531): 2867 - 2880. [Abstract] [Full Text] [PDF] R. Bhattacharya, J. Kwon, X. Li, E. Wang, S. Patra, J. P. Bida, Z. Bajzer, L. Claesson-Welsh, and D. Mukhopadhyay Distinct role of PLC{beta}3 in VEGF-mediated directional migration and vascular sprouting J. Cell Sci., April 1, 2009; 122(7): 1025 - 1034. [Abstract] [Full Text] [PDF] Y. Alsayed, H. Ngo, J. Runnels, X. Leleu, U. K. Singha, C. M. Pitsillides, J. A. Spencer, T. Kimlinger, J. M. Ghobrial, X. Jia, et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma Blood, April 1, 2007; 109(7): 2708 - 2717. [Abstract] [Full Text] [PDF]

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