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The Rho inhibitor p190RhoGAP controls VEGFR2 transcription and angiogenesis in vitro through antagonism between GATA2 and TFII‐I
Author(s) -
Mammoto Akiko,
Mammoto Tadanori,
Ingber Donald
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.471.9
Subject(s) - angiogenesis , microbiology and biotechnology , transcription factor , cdc42 , vascular endothelial growth factor , gata2 , chemistry , cancer research , vascular endothelial growth factor a , biology , signal transduction , stem cell , vegf receptors , biochemistry , haematopoiesis , gene
Angiogenesis can be controlled by mechanical interactions between cells and extracellular matrix (ECM) mediated by the Rho GTPase signaling pathway, as well as by the soluble angiogenic factor, vascular endothelial growth factor (VEGF) that stimulates capillary blood vessel development by binding VEGFR2 receptors on the endothelial cell surface. Here we show that the Rho inhibitor, p190RhoGAP, regulates angiogenesis by controlling VEGFR2 expression, and that it produces this effect by modulating cross antagonism between two transcription factors ‐ TFII‐I and GATA2 – that regulate VEGFR2 transcription. p190Rho GAP binds to both TFII‐I and GATA2, and sequesters them in the cytoplasm, thereby preventing VEGFR2 expression . TFII‐I decreases VEGFR2 promoter activity and expression as well as migration and capillary tube formation by human microvascular endothelial cells, whereas GATA2 produces the opposite effects, and antagonizes TFII‐I. Thus, the balance between TFII‐I and GATA2 appears to be critical for regulation of vascular network formation, and it appears to be controlled by p190RhoGAP that can sense both chemical and mechanical cues in the tissue microenvironment. (Supported by NIH)