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踝蛋白2在牵张力产生、肿瘤转移和心血管完整性中的作用。

Roles of Talin2 in Traction Force Generation, Tumor Metastasis and Cardiovascular Integrity.

作者信息

Qi Lei, Kolodziej Tomasz, Rajfur Zenon, Huang Cai

机构信息

Markey Cancer Center, University of Kentucky, Lexington, KY 40536, United States.

Department of Biosystems Physics, Jagiellonian University, Krakow, Poland.

出版信息

Curr Protein Pept Sci. 2018;19(11):1071-1078. doi: 10.2174/1389203719666180809094731.

Abstract

There are two vertebrate talin genes, TLN1 and TLN2, which encode talin1 and talin2. Talin1 governs integrin activation, thus regulating focal adhesion (FA) assembly, cell migration and invasion, but the biological function of talin2 remains to be elucidated and not too long ago talin2 was presumed to function redundantly with talin1. Recent studies have shown distinct differences between talin2 and talin1. The promoter of TLN2 is different from that of TLN1 in their size and binding to different transcription factors. Talin2 has a higher affinity to β -integrins than talin1. Talin2 regulates traction force generation, focal adhesion dynamics and invadopodium formation, thus controlling tumor cell migration, invasion and metastasis. Also, talin2 is enriched in the myotendinous junction (MTJ) in striated muscle, costameres and intercalated disks (ICDs) of cardiac myofibrils, and atherosclerotic plaques of blood vessels, thus regulating cardiovascular integrity. In this review, we discuss the differences between talin1 and talin2, in genome, protein expression pattern, affinity with integrins, traction force generation, and provide a glance at the roles of talin2 in cancer cell invasion and cardiovascular function.

摘要

脊椎动物中有两个踝蛋白基因,TLN1和TLN2,它们分别编码踝蛋白1和踝蛋白2。踝蛋白1调控整合素激活,从而调节黏着斑(FA)组装、细胞迁移和侵袭,但是踝蛋白2的生物学功能仍有待阐明,并且不久之前人们还认为踝蛋白2与踝蛋白1功能冗余。最近的研究表明踝蛋白2和踝蛋白1之间存在明显差异。TLN2的启动子在大小以及与不同转录因子的结合方面不同于TLN1的启动子。踝蛋白2对β-整合素的亲和力高于踝蛋白1。踝蛋白2调节牵引力产生、黏着斑动态变化和侵袭伪足形成,从而控制肿瘤细胞迁移、侵袭和转移。此外,踝蛋白2在横纹肌的肌腱连接点(MTJ)、心肌原纤维的肌小节和闰盘(ICD)以及血管的动脉粥样硬化斑块中富集,从而调节心血管完整性。在这篇综述中,我们讨论了踝蛋白1和踝蛋白2在基因组、蛋白质表达模式、与整合素的亲和力、牵引力产生方面的差异,并简要介绍了踝蛋白2在癌细胞侵袭和心血管功能中的作用。

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