Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting

Resham Bhattacharya, Junhye Kwon, Xiujuan Li, Enfeng Wang, Sujata Patra, John Paul Bida, Zeijko Bajzer, Lena Claesson-Welsh, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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 PLCγ1 - 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 PLCβ3, and this was confirmed in an ex vivo embryoid body model. Knockdown of PLCβ3 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 PLCβ3 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.

Original languageEnglish (US)
Pages (from-to)1025-1034
Number of pages10
JournalJournal of cell science
Volume122
Issue number7
DOIs
StatePublished - Apr 1 2009

Keywords

  • Endothelial signaling
  • Migration
  • PLCβ3
  • Proliferation

ASJC Scopus subject areas

  • Cell Biology

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    Bhattacharya, R., Kwon, J., Li, X., Wang, E., Patra, S., Bida, J. P., Bajzer, Z., Claesson-Welsh, L., & Mukhopadhyay, D. (2009). Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting. Journal of cell science, 122(7), 1025-1034. https://doi.org/10.1242/jcs.041913