The interaction of SRC kinase with beta3 integrin tails: a potential therapeutic target in thrombosis and cancer.
The interaction of SRC kinase with beta3 integrin tails: a potential therapeutic target in thrombosis and cancer.
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DOI：
10.1100/tsw.2010.114
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发表时间：
2010-06-15
影响因子：
--
通讯作者：
Danen EH
中科院分区：
文献类型：
--
作者：
Huveneers S;Danen EH
Src家族激酶的激活是许多细胞类型中整合素粘附信号传导下游的重要事件。整合素和Src家族激酶之间特别有趣的联系首次在血小板中发现，其中αIIbβ3整合素与c-Src的选择性直接相互作用通过β3整合素亚基的胞质尾部局部聚集促进c-Src的完全激酶激活。相同的整合素β3-c-Src相互作用不仅驱动血小板聚集，而且还促进c-Src的致癌潜力并通过表达αvβ3的肿瘤细胞驱动肿瘤生长，这可以解释为什么在相同的肿瘤类型中经常发现c-Src活性增加和整合素αvβ3水平升高。此外，来自患者材料和体内研究的最新证据强烈表明，这种由c-Src和αvβ3组成的致癌信号复合物是人类肿瘤进展的基础。在这里，我们概述了β3-c-Src相互作用及其对血小板和肿瘤细胞信号传导的影响，我们提到了旨在破坏β3-c-Src相互作用以达到抗血栓和抗癌目的的治疗干预的可能性。
Activation of Src family kinases is an important event downstream of integrin adhesion signaling in many cell types. A particularly intriguing connection between an integrin and a Src family kinase was first discovered in platelets, where the selective direct interaction of αIIbβ3 integrins with c-Src promotes full kinase activation of c-Src through its local clustering by the cytoplasmic tail of the β3 integrin subunit. The same integrin β3-c-Src interaction not only drives platelet aggregation, but it also promotes the oncogenic potential of c-Src and drives tumor growth by αvβ3-expressing tumor cells, which may explain why increased activity of c-Src and elevated levels of integrin αvβ3 are often found in the same tumor types. Moreover, recent evidence from patient material and in vivo studies strongly indicate that this oncogenic signaling complex, consisting of c-Src and αvβ3, underlies tumor progression of human tumors. Here, we give an overview of the β3-c-Src interaction and its implications for signaling in platelets and tumor cells, and we mention the possibilities for therapeutic intervention that is aimed at disrupting the β3-c-Src interaction for antithrombotic and anticancer purposes.
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影响因子：
8.4
作者：
Putnam, Andrew J.;Schulz, Veronique V.;Miranti, Cindy K.
通讯作者：
Miranti, Cindy K.
影响因子：
20.3
作者：
Su, Xiaoyu;Mi, Jianqing;Xi, Xiaodong
通讯作者：
Xi, Xiaodong
DOI：
10.1111/j.1349-7006.2000.tb00958.x
发表时间：
2000-04-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Sugimura, M;Kobayashi, K;Kudo, R
通讯作者：
Kudo, R
影响因子：
21.3
作者：
Felsenfeld, DP;Schwartzberg, PL;Sheetz, MP
通讯作者：
Sheetz, MP
DOI：
10.1073/pnas.0903035106
发表时间：
2009-06-30
影响因子：
11.1
作者：
Lorger, Mihaela;Krueger, Joseph S.;Felding-Habermann, Brunhilde
通讯作者：
Felding-Habermann, Brunhilde