Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1

Jia Hong, Robert C. Doebele, Mark W. Lingen, Lawrence A. Quilliam, Wei Jen Tang, Marsha Rich Rosner

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Angiogenesis involves the assembly of endothelial cells into capillaries from a pre-existing vasculature. Because abnormal angiogenesis is a hallmark of many cancers, it is critical to find factors that control this process. Endothelial cells are enriched in the anthrax receptor; we therefore determined the effect of anthrax edema toxin (ET), an adenylyl cyclase, on chemotaxis. cAMP generated by ET does not block proliferation or survival but causes cytoskeletal changes and inhibits chemotaxis by primary human microvascular endothelial cells (HMVECs). These effects are due to the action of a downstream cAMP effector, Epac, a guanine nucleotide exchange-activating protein for Rap1 (RAP1-GEF). ET induces transcription of Epac-related activators of Rap1, Epac2 (RapGEF4), and MR-GEF/RapGEF5. Similar to ET, activated Epac or Rap1 induces cytoskeletal changes and blocks chemotaxis in human endothelial cells. These results identify Epac and Rap1 as key regulators of signaling cascades leading to endothelial cell chemotaxis.

Original languageEnglish (US)
Pages (from-to)19781-19787
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number27
DOIs
StatePublished - Jul 6 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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