c-Jun N-terminal kinase activation is required for the inhibition of neovascularization by thrombospondin-1

Benilde Jiménez*, Olga V. Volpert, Frank Reiher, Lufen Chang, Alberto Mũoz, Michael Karin, Noël Bouck

*Corresponding author for this work

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis that acts directly on endothelial cells via the CD36 surface receptor molecule to halt their migration, proliferation, and morphogenesis in vitro and to block neovascularization in vivo. Here we show that inhibitory signals elicited by TSP-1 did not alter the ability of inducers of angiogenesis to activate p42 and p44 mitogen-activated protein kinase (MAPK). Rather, TSP-1 induced a rapid and transient activation of c-Jun N-terminal kinases (JNK). JNK activation by TSP-1 required engagement of CD36, as it was blocked by antagonistic CD36 antibodies and stimulated by short anti-angiogenic peptides derived from TSP-1 that act exclusively via CD36. TSP-1 inhibition of corneal neovascularization induced by bFGF was severely impaired in mice null for JNK-1, pointing to a critical role for this stress-activated kinase in the inhibition of neovascularization by TSP-1.

Original languageEnglish (US)
Pages (from-to)3443-3448
Number of pages6
JournalOncogene
Volume20
Issue number26
DOIs
StatePublished - Jun 7 2001

Keywords

  • Anti-angiogenic signalling
  • CD36
  • JNK
  • Thrombospondin
  • Tumor angiogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Jiménez, B., Volpert, O. V., Reiher, F., Chang, L., Mũoz, A., Karin, M., & Bouck, N. (2001). c-Jun N-terminal kinase activation is required for the inhibition of neovascularization by thrombospondin-1. Oncogene, 20(26), 3443-3448. https://doi.org/10.1038/sj.onc.1204464