Torgler Catherine N, Narasimha Maithreyi, Knox Andrea L, Zervas Christos G, Vernon Matthew C, Brown Nicholas H
Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Anatomy, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
Dev Cell. 2004 Mar;6(3):357-69. doi: 10.1016/s1534-5807(04)00055-3.
We report the functional characterization of the Drosophila ortholog of tensin, a protein implicated in linking integrins to the cytoskeleton and signaling pathways. A tensin null was generated and is viable with wing blisters, a phenotype characteristic of loss of integrin adhesion. In tensin mutants, mechanical abrasion is required during wing expansion to cause wing blisters, suggesting that tensin strengthens integrin adhesion. The localization of tensin requires integrins, talin, and integrin-linked kinase. The N-terminal domain and C-terminal PTB domain of tensin provide essential recruitment signals. The intervening SH2 domain is not localized on its own. We suggest a model where tensin is recruited to sites of integrin adhesion via its PTB and N-terminal domains, localizing the SH2 domain so that it can interact with phosphotyrosine-containing proteins, which stabilize the integrin link to the cytoskeleton.
我们报道了果蝇中张力蛋白直系同源物的功能特征，张力蛋白是一种与整合素连接细胞骨架和信号通路相关的蛋白质。构建了一个张力蛋白缺失突变体，它具有翅泡且可存活，翅泡是整合素黏附丧失的典型表型。在张力蛋白突变体中，翅扩展过程中需要机械摩擦才能导致翅泡形成，这表明张力蛋白增强了整合素黏附。张力蛋白的定位需要整合素、踝蛋白和整合素连接激酶。张力蛋白的N端结构域和C端PTB结构域提供了关键的招募信号。中间的SH2结构域自身并不定位。我们提出了一个模型，即张力蛋白通过其PTB和N端结构域被招募到整合素黏附位点，使SH2结构域定位，以便它能与含磷酸酪氨酸的蛋白质相互作用，从而稳定整合素与细胞骨架的连接。
