Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase

Xavier Cullere, Sunil K. Shaw, Lorna Andersson, Junichi Hirahashi, Francis W. Luscinskas, Tanya N. Mayadas

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

Endothelial cell-cell junctional proteins and cortical actin are of central importance for regulating vascular permeability. Rap1, a member of the Ras family of GTPases, is enriched at endothelial cell-cell contacts and activated by cyclic AMP (cAMP) through a PKA-independent pathway. Activation of a cAMP-inducible gua nine-exchange factor for Rap, Epac, results in markedly enhanced basal endothelial barrier function by increasing cortical actin and subsequent redistribution of adherens and tight junctional molecules to cell-cell contacts. Activation of Epac also counteracts thrombin-induced hyperpermeability through down-regula tion of Rho GTPase activation, suggesting cross-talk between Rap and Rho GTPases. Thus, Epac/Rap activation represents a new pathway for regulating endothelial cell barrier function.

Original languageEnglish
Pages (from-to)1950-1955
Number of pages6
JournalBlood
Volume105
Issue number5
DOIs
Publication statusPublished - 2005 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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