Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P39060 (
endostatin
)
2,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endostatin, a fragment of
collagen XVIII
, is a potent anti-angiogenic protein, but the molecular mechanism of its action is not yet clear. We examined the effects of
endostatin
on the biological and biochemical activities of vascular endothelial growth factor (VEGF). Endostatin blocked VEGF-induced tyrosine phosphorylation of KDR/Flk-1 and activation of ERK, p38 MAPK, and
p125
(FAK) in human umbilical vein endothelial cells. Endostatin also inhibited the binding of VEGF(165) to both endothelial cells and purified extracellular domain of KDR/Flk-1. Moreover, the binding of VEGF(121) to KDR/Flk-1 and VEGF(121)-stimulated ERK activation were blocked by
endostatin
. The direct interaction between
endostatin
and KDR/Flk-1 was confirmed by affinity chromatography. However,
endostatin
did not bind to VEGF. Our findings suggest that a direct interaction of
endostatin
with KDR/Flk-1 may be involved in the inhibitory function of
endostatin
toward VEGF actions and responsible for its potent anti-angiogenic and anti-tumor activities in vivo.
...
PMID:Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1. 1202 87
