Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity

被引：51

作者：

Alam, A

Herault, JP

Barron, P

Favier, B

Fons, P

Delesque-Touchard, N

Senegas, I

Laboudie, P

Bonnin, J

Cassan, C

Savi, P

Ruggeri, B

Carmeliet, P

Bono, FO

Herbert, JM ^{[1
]}

机构：

[1] Sanofi Synthelabo Res, Cardiovasc Dept, Toulouse, France

[2] Cephalon Inc, W Chester, PA USA

[3] Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 324卷 / 02期

关键词：

angiogenesis; lymphanaiogenesis; CEP-5214; tyrosine kinase; VEGFR-2; VEGFR-3;

D O I：

10.1016/j.bbrc.2004.08.237

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

VEGFR-3 is essential for vascular development and maintenance of lymphatic vessel's integrity. Little is known about its cooperative effect with other receptors of the same family. Contrary to VEGFR-2, stimulation of VEGFR-3 by VEGF-C and -D failed to enhance its phosphorylation either in HEK293T or in PAE cells. These ligands were unable to induce angiogenesis of PAEC expressing VEGFR-3 alone. In the presence of VEGFR-2, VEGF-C and -D induced heterodimerization of VEGFR-3 with VEGFR-2. This heterodimerization was associated with enhanced VEGFR-3 phosphorylation and subsequent cellular responses as evidenced by the formation of capillary-like structures in PAE cells and proliferation of primary human endothelial cells expressing both receptors. Taken together, these results show for the first time that VEGFR-3 needs to be associated to VEGFR-2 to induce ligand-dependent cellular responses. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：909 / 915

页数：7

共 30 条

[1] Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy [J].