TY - JOUR
T1 - Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting
AU - Bhattacharya, Resham
AU - Kwon, Junhye
AU - Li, Xiujuan
AU - Wang, Enfeng
AU - Patra, Sujata
AU - Bida, John Paul
AU - Bajzer, Zeijko
AU - Claesson-Welsh, Lena
AU - Mukhopadhyay, Debabrata
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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.
AB - 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.
KW - Endothelial signaling
KW - Migration
KW - PLCβ3
KW - Proliferation
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UR - http://www.scopus.com/inward/citedby.url?scp=66849115292&partnerID=8YFLogxK
U2 - 10.1242/jcs.041913
DO - 10.1242/jcs.041913
M3 - Article
C2 - 19295129
AN - SCOPUS:66849115292
SN - 0021-9533
VL - 122
SP - 1025
EP - 1034
JO - Journal of cell science
JF - Journal of cell science
IS - 7
ER -