Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2002, PMID: 12029087

Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1.

Kim, Young-Mi; Hwang, Sewook; Kim, Young-Myoeng; Pyun, Bo-Jeong; Kim, Tae-Yoon; Lee, Seung-Taek; Gho, Yong Song; Kwon, Young-Guen

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.

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Text Mining Data

MAPK → 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 "

MAPK → KDR/Flk-1: " 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 "

ERK → 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 "

ERK → KDR/Flk-1: " 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 "

KDR/Flk-1 → 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 "

KDR/Flk-1 → p125(FAK): " 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 "

p125(FAK) → 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 "

Manually curated Databases

  • IRef Biogrid Interaction: KDR — COL18A1 (direct interaction, pull down)
  • IRef Hprd Interaction: COL18A1 — KDR (in vitro)
  • MIPS Negatome - no physical interaction between proteins Interaction: COL18A1 — VEGFA (Absence of interaction, affinity chromatography technologies)
In total, 2 gene pairs are associated to this article in curated databases