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    Ann N Y Acad Sci. 2000 May;902:201-5; discussion 205-7.

    Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction.

    Sato Y, Kanno S, Oda N, Abe M, Ito M, Shitara K, Shibuya M.

    Department of Vascular Biology, Tohoku University, Sendai, Japan. y-sato@idac.tohoku.ac.jp

    The properties of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF in human umbilical vein endothelial cells (HUVECs) were investigated by using two newly developed blocking monoclonal antibodies (mAbs) against Flt-1 and KDR. VEGF stimulated the expression of transcription factor Ets-1 as well as matrix metalloproteinase-1 (MMP-1) and Flt-1 in HUVECs. The KDR/Flt-1 heterodimer and the KDR homodimer mediate the expression of Ets-1, MMP-1, and Flt-1. VEGF also stimulated DNA synthesis and migration of HUVECs. DNA synthesis is mediated by the same signaling system as the expression of Ets-1. In contrast, cell migration is regulated by two distinct signaling systems. The Flt-1 homodimer is required for actin reorganization. The KDR/Flt-1 heterodimer and the KDR homodimer are required for the assembly of vinculin in focal adhesion plaque by regulating the phosphorylation of focal adhesion kinase (FAK) and paxillin.

    PMID: 10865839 [PubMed - indexed for MEDLINE]

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