Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo

被引：365

作者：

Orsenigo, Fabrizio ^{[1
]}

Giampietro, Costanza ^{[1
]}

Ferrari, Aldo ^{[2
]}

Corada, Monica ^{[1
]}

Galaup, Ariane ^{[3
]}

Sigismund, Sara ^{[1
]}

Ristagno, Giuseppe ^{[4
]}

Maddaluno, Luigi ^{[1
]}

Koh, Gou Young ^{[5
]}

Franco, Davide ^{[2
]}

Kurtcuoglu, Vartan ^{[2
,6
]}

Poulikakos, Dimos ^{[2
]}

Baluk, Peter ^{[7
]}

McDonald, Donald ^{[7
]}

Lampugnani, Maria Grazia ^{[4
]}

Dejana, Elisabetta ^{[1
,8
]}

机构：

[1] FIRC Inst Mol Oncol, I-20139 Milan, Italy

[2] Swiss Fed Inst Technol, Dept Mech & Proc Engn, CH-8092 Zurich, Switzerland

[3] Coll France, INSERM, F-75005 Paris, France

[4] Mario Negri Inst Pharmacol Res, Dept Cardiovasc Res, I-20156 Milan, Italy

[5] Korea Adv Inst Sci & Technol, Dept Physiol, Taejon 305701, South Korea

[6] Univ Zurich, Inst Physiol, Interface Grp, CH-8057 Zurich, Switzerland

[7] Univ Calif San Francisco, Cardiovasc Res Inst, Ctr Comprehens Canc, Dept Anat, San Francisco, CA 94143 USA

[8] Univ Milan, Dept Biotechnol & Biomol Sci, Sch Sci, I-20133 Milan, Italy

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

基金：

欧洲研究理事会;

关键词：

ARTERIAL BRANCHING MORPHOGENESIS; ENDOTHELIAL-CELL JUNCTIONS; TYROSINE PHOSPHORYLATION; DEPENDENT ENDOCYTOSIS; ADHERENS JUNCTIONS; BARRIER FUNCTION; TIGHT JUNCTIONS; GROWTH-FACTOR; SRC; ANGIOPOIETIN-1;

D O I：

10.1038/ncomms2199

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents.

引用

页数：15

共 60 条

[1] Ubiquitin in trafficking: The network at work [J].