Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells.
Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells.
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DOI：
10.1083/jcb.200709127
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发表时间：
2008-04-07
影响因子：
7.8
通讯作者：
Miyazawa, Keiji
中科院分区：
文献类型：
--
作者：
Kawasaki, Kyoko;Watabe, Tetsuro;Sase, Hitoshi;Hirashima, Masanori;Koide, Hiroshi;Morishita, Yasuyuki;Yuki, Keiko;Sasaoka, Toshikuni;Suda, Toshio;Katsuki, Motoya;Miyazono, Kohei;Miyazawa, Keiji
血管内皮生长因子受体2 （VEGFR2）传递对血管发生至关重要的信号，包括血管祖细胞的增殖、迁移和分化。胚胎干细胞衍生的VEGFR2+中胚层细胞在血小板衍生生长因子(PDGF) -BB或血清的存在下分化为壁系，但在VEGF-A的作用下分化为内皮系。我们发现，通过法尼基转移酶抑制剂或敲低技术抑制H-Ras功能可选择性抑制vegf - a诱导的内皮特异性。离体全胚胎培养实验和H-ras - / -小鼠分析也支持这一结论。此外，VEGFR2+祖细胞中组成型活性H-Ras[G12V]的表达通过细胞外信号相关激酶（Erk）途径导致内皮分化。治疗后5分钟，VEGF-A和PDGF-BB均激活了VEGFR2+祖细胞中的Ras。然而，VEGF-A，而不是PDGF-BB，在诱导内皮标志物之前，在治疗后6-9小时激活Ras。因此，VEGF-A激活了时间上不同的Ras-Erk信号，以指导VEGFR2+血管祖细胞的内皮特异性。
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.
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影响因子：
56.9
作者：
Joneson, T;White, MA;BarSagi, D
通讯作者：
BarSagi, D
在两种血管生成途径中，差异alphav整联蛋白介导的RAS-ERK信号传导。
DOI：
10.1083/jcb.200304105
发表时间：
2003-09-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hood JD;Frausto R;Kiosses WB;Schwartz MA;Cheresh DA
通讯作者：
Cheresh DA
影响因子：
8
作者：
Ise, K;Nakamura, K;Katsuki, M
通讯作者：
Katsuki, M
影响因子：
5.3
作者：
Hiratsuka, S;Kataoka, Y;Shibuya, M
通讯作者：
Shibuya, M
影响因子：
8
作者：
Klint, P;Kanda, S;Claesson-Welsh, L
通讯作者：
Claesson-Welsh, L