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Distinct role of PLC{beta}3 in VEGF-mediated directional migration and vascular sprouting
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2009 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 122, no 7, 1025-1034 p.Article in journal (Refereed) Published
Abstract [en]

Endothelial cell proliferation and migration is essential to angiogenesis. Typically, proliferation and chemotaxis of endothelial cells is driven by growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF activates phospholipases (PLCs) - specifically PLCgamma1 - that are important for tubulogenesis, differentiation and DNA synthesis. However, we show here that VEGF, specifically through VEGFR2, induces phosphorylation of two serine residues on PLCbeta3, and this was confirmed in an ex vivo embryoid body model. Knockdown of PLCbeta3 in HUVEC cells affects IP3 production, actin reorganization, migration and proliferation; whereas migration is inhibited, proliferation is enhanced. Our data suggest that enhanced proliferation is precipitated by an accelerated cell cycle, and decreased migration by an inability to activate CDC42. Given that PLCbeta3 is typically known as an effector of heterotrimeric G-proteins, our data demonstrate a unique crosstalk between the G-protein and receptor tyrosine kinase (RTK) axes and reveal a novel molecular mechanism of VEGF signaling and, thus, angiogenesis.

Place, publisher, year, edition, pages
2009. Vol. 122, no 7, 1025-1034 p.
Keyword [en]
Migration, Proliferation, Endothelial signaling, PLC beta 3
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-100993DOI: 10.1242/jcs.041913ISI: 000264342000017PubMedID: 19295129OAI: oai:DiVA.org:uu-100993DiVA: diva2:211493
Available from: 2009-04-15 Created: 2009-04-15 Last updated: 2010-08-12Bibliographically approved

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Claesson-Welsh, Lena
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