Evidence of a common mechanism of disassembly of adherens junctions through Gα13 targeting of VE-cadherin

Haixia Gong, Xiaopei Gao, Shaoting Feng, M. Rizwan Siddiqui, Alexander Garcia, Marcelo G. Bonini, Yulia Komarova, Stephen M. Vogel, Dolly Mehta, Asrar B. Malik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


The heterotrimeric G protein Gα13 transduces signals from G protein-coupled receptors (GPCRs) to induce cell spreading, differentiation, migration, and cell polarity. Here, we describe a novel GPCR-independent function of Gα13 in regulating the stability of endothelial cell adherens junctions (AJs). We observed that the oxidant H2O2, which is released in response to multiple proinflammatory mediators, induced the interaction of Gα13 with VE-cadherin. Gα13 binding to VE-cadherin in turn induced Src activation and VE-cadherin phosphorylation at Tyr 658, the p120-catenin binding site thought to be responsible for VE-cadherin internalization. Inhibition of Gα13-VE-cadherin interaction using an interfering peptide derived from the Gα13 binding motif on VE-cadherin abrogated the disruption of AJs in response to inflammatory mediators. These studies identify a unique role of Gα13 binding to VE-cadherin in mediating VE-cadherin internalization and endothelial barrier disruption and inflammation.

Original languageEnglish (US)
Pages (from-to)579-591
Number of pages13
JournalJournal of Experimental Medicine
Issue number3
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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