Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells

Kyoko Kawasaki, Tetsuro Watabe, Hitoshi Sase, Masanori Hirashima, Hiroshi Koide, Yasuyuki Morishita, Keiko Yuki, Toshikuni Sasaoka, Toshio Suda, Motoya Katsuki, Kohei Miyazono, Keiji Miyazawa

研究成果: Article査読

41 被引用数 (Scopus)

抄録

Vascular endothelial growth factor receptor 2 (VEGFR2) transmits signals of crucial importance to vasculogenesis, including proliferation, migration, and differentiation of vascular progenitor cells. Embryonic stem cell-derived VEGFR2+ mesodermal cells differentiate into mural lineage in the presence of platelet derived growth factor (PDGF)-BB or serum but into endothelial lineage in response to VEGF-A. We found that inhibition of H-Ras function by a farnesyltransferase inhibitor or a knockdown technique results in selective suppression of VEGF-A-induced endothelial specification. Experiments with ex vivo whole-embryo culture as well as analysis of H-ras-/- mice also supported this conclusion. Furthermore, expression of a constitutively active H-Ras[G12V] in VEGFR2+ progenitor cells resulted in endothelial differentiation through the extracellular signal-related kinase (Erk) pathway. Both VEGF-A and PDGF-BB activated Ras in VEGFR2+ progenitor cells 5 min after treatment. However, VEGF-A, but not PDGF-BB, activated Ras 6-9 h after treatment, preceding the induction of endothelial markers. VEGF-A thus activates temporally distinct Ras-Erk signaling to direct endothelial specification of VEGFR2+ vascular progenitor cells.

本文言語English
ページ(範囲)131-141
ページ数11
ジャーナルJournal of Cell Biology
181
1
DOI
出版ステータスPublished - 2008 4 7

ASJC Scopus subject areas

  • 細胞生物学

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