Differential alphav integrin-mediated Ras-ERK signaling during two pathways of angiogenesis.
Differential alphav integrin-mediated Ras-ERK signaling during two pathways of angiogenesis.
复制标题
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
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发表时间：
2003-09-01
期刊：
影响因子：
--
通讯作者：
Cheresh DA
中科院分区：
文献类型：
--
作者：
Hood JD;Frausto R;Kiosses WB;Schwartz MA;Cheresh DA
αvβ3和αvβ5的拮抗剂分别响应于bFGF和VEGF而破坏血管生成。在这里，我们表明，这些αv整合素差异有助于持续Ras细胞外信号相关激酶（Ras-ERK）信号在血管中，内皮细胞存活和血管生成的要求。抑制FAK或αvβ5破坏鸡胚绒毛尿囊膜上VEGF介导的Ras和c-Raf活性，而阻断FAK或整合素αvβ3对bFGF介导的Ras活性没有影响，但抑制c-Raf活化。此外，逆转录病毒递送活性Ras或c-Raf促进ERK活性和血管生成，抗αvβ5阻断Ras上游，而抗αvβ3阻断Ras下游，但阻断c-Raf上游。bFGF/αvβ3对c-Raf的激活不仅依赖于FAK，还需要p21激活的激酶依赖的丝氨酸338磷酸化，而VEGF介导的c-Raf的磷酸化/激活依赖于Src，而不依赖于Pak。因此，整合素αvβ3和αvβ5差异调节Ras-ERK途径，解释了两种血管生成途径中不同的血管反应。
Antagonists of αvβ3 and αvβ5 disrupt angiogenesis in response to bFGF and VEGF, respectively. Here, we show that these αv integrins differentially contribute to sustained Ras-extracellular signal–related kinase (Ras-ERK) signaling in blood vessels, a requirement for endothelial cell survival and angiogenesis. Inhibition of FAK or αvβ5 disrupted VEGF-mediated Ras and c-Raf activity on the chick chorioallantoic membrane, whereas blockade of FAK or integrin αvβ3 had no effect on bFGF-mediated Ras activity, but did suppress c-Raf activation. Furthermore, retroviral delivery of active Ras or c-Raf promoted ERK activity and angiogenesis, which anti-αvβ5 blocked upstream of Ras, whereas anti-αvβ3 blocked downstream of Ras, but upstream of c-Raf. The activation of c-Raf by bFGF/αvβ3 not only depended on FAK, but also required p21-activated kinase-dependent phosphorylation of serine 338 on c-Raf, whereas VEGF-mediated c-Raf phosphorylation/activation depended on Src, but not Pak. Thus, integrins αvβ3 and αvβ5 differentially regulate the Ras-ERK pathway, accounting for distinct vascular responses during two pathways of angiogenesis.
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影响因子：
9.2
作者：
Giroux, S;Tremblay, M;Charron, J
通讯作者：
Charron, J
影响因子：
4.8
作者：
He, H;Venema, VJ;Caldwell, RB
通讯作者：
Caldwell, RB
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.1073/pnas.93.18.9764
发表时间：
1996-09-03
影响因子：
11.1
作者：
Friedlander, M;Theesfeld, CL;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
9.2
作者：
Chaudhary, A;King, WG;Brugge, JS
通讯作者：
Brugge, JS