Cross Talk among TGF-β Signaling Pathways, Integrins, and the Extracellular Matrix
Cross Talk among TGF-β Signaling Pathways, Integrins, and the Extracellular Matrix
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DOI：
10.1101/cshperspect.a005017
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发表时间：
2011-11-01
影响因子：
7.2
通讯作者：
Sheppard, Dean
中科院分区：
文献类型：
--
作者：
Munger, John S.;Sheppard, Dean
生长因子 TGF-β 在由三种蛋白组成的潜在复合物中分泌：TGF-β、抑制剂（潜伏相关蛋白，LAP，源自 TGF-β 前肽）和 ECM 结合蛋白（潜在 TGF-β 结合蛋白之一，或 LTBP）。 LTBP 与原纤维蛋白和其他 ECM 成分相互作用，从而发挥定位 ECM 中潜在 TGF-β 的作用。 LAP 含有一个整合素结合位点 (RGD)，一些 RGD 结合整合素能够通过结合该位点激活潜在的 TGF-β。整合素介导的激活剂有缺陷的突变小鼠，以及原纤维蛋白基因突变的人类和小鼠，显示了 ECM 和整合素在调节 TGF-β 信号传导中的关键作用。
The growth factor TGF-beta is secreted in a latent complex consisting of three proteins: TGF-beta, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-beta propeptide) and an ECM-binding protein (one of the latent TGF-beta binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-beta in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-beta through binding this site. Mutant mice defective in integrin-mediated activators, and humans and mice with fibrillin gene mutations, show the critical role of ECM and integrins in regulating TGF-beta signaling.