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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)131-141
Number of pages11
JournalJournal of Cell Biology
Volume181
Issue number1
DOIs
Publication statusPublished - 2008 Apr 7

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Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor A
Blood Vessels
Stem Cells
Phosphotransferases
Farnesyltranstransferase
Embryonic Stem Cells
Embryonic Structures
Serum
platelet-derived growth factor BB

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kawasaki, K., Watabe, T., Sase, H., Hirashima, M., Koide, H., Morishita, Y., ... Miyazawa, K. (2008). Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells. Journal of Cell Biology, 181(1), 131-141. https://doi.org/10.1083/jcb.200709127

Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells. / Kawasaki, Kyoko; Watabe, Tetsuro; Sase, Hitoshi; Hirashima, Masanori; Koide, Hiroshi; Morishita, Yasuyuki; Yuki, Keiko; Sasaoka, Toshikuni; Suda, Toshio; Katsuki, Motoya; Miyazono, Kohei; Miyazawa, Keiji.

In: Journal of Cell Biology, Vol. 181, No. 1, 07.04.2008, p. 131-141.

Research output: Contribution to journalArticle

Kawasaki, K, Watabe, T, Sase, H, Hirashima, M, Koide, H, Morishita, Y, Yuki, K, Sasaoka, T, Suda, T, Katsuki, M, Miyazono, K & Miyazawa, K 2008, 'Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells', Journal of Cell Biology, vol. 181, no. 1, pp. 131-141. https://doi.org/10.1083/jcb.200709127
Kawasaki K, Watabe T, Sase H, Hirashima M, Koide H, Morishita Y et al. Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells. Journal of Cell Biology. 2008 Apr 7;181(1):131-141. https://doi.org/10.1083/jcb.200709127
Kawasaki, Kyoko ; Watabe, Tetsuro ; Sase, Hitoshi ; Hirashima, Masanori ; Koide, Hiroshi ; Morishita, Yasuyuki ; Yuki, Keiko ; Sasaoka, Toshikuni ; Suda, Toshio ; Katsuki, Motoya ; Miyazono, Kohei ; Miyazawa, Keiji. / Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells. In: Journal of Cell Biology. 2008 ; Vol. 181, No. 1. pp. 131-141.
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