Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1.
SCIE
SCOPUS
- Title
- Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1.
- Authors
- Kim, YM; Hwang, S; Kim, YM; Pyun, BJ; Kim, TY; Lee, ST; Gho, YS; Kwon, YG
- Date Issued
- 2002-08-02
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLO
- Abstract
- 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.
- Keywords
- TUMOR-GROWTH; CELL PROLIFERATION; NITRIC-OXIDE; ANGIOGENESIS; KINASE; BINDING; MECHANISMS; MIGRATION; APOPTOSIS; RECEPTORS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28393
- DOI
- 10.1074/JBC.M2027712
- ISSN
- 0021-9258
- Article Type
- Article
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 277, no. 31, page. 27872 - 27879, 2002-08-02
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