Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1

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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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

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Endothelial cells
Chemotaxis
Edema
Endothelial Cells
Anthrax
Guanine Nucleotides
Transcription
Adenylyl Cyclases
anthrax toxin
Survival
Neoplasms
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1. / Hong, Jia; Doebele, Robert C.; Lingen, Mark W.; Quilliam, Lawrence; Tang, Wei Jen; Rosner, Marsha Rich.

In: Journal of Biological Chemistry, Vol. 282, No. 27, 06.07.2007, p. 19781-19787.

Research output: Contribution to journalArticle

Hong, Jia ; Doebele, Robert C. ; Lingen, Mark W. ; Quilliam, Lawrence ; Tang, Wei Jen ; Rosner, Marsha Rich. / Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 27. pp. 19781-19787.
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