c-Jun N-terminal kinase activation is required for the inhibition of neovascularization by thrombospondin-1.
Oncogene
; 20(26): 3443-8, 2001 Jun 07.
Article
in En
| MEDLINE
| ID: mdl-11423995
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neovascularization, Physiologic
/
Thrombospondin 1
/
Mitogen-Activated Protein Kinases
/
Angiogenesis Inhibitors
/
MAP Kinase Signaling System
Limits:
Animals
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2001
Document type:
Article
Affiliation country:
España