The LFA-1-associated molecule PTA-1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large
The LFA-1-associated molecule PTA-1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large
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DOI：
10.1074/jbc.m401040200
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发表时间：
2004-08-06
影响因子：
4.8
通讯作者：
Burns, GF
中科院分区：
文献类型：
--
作者：
Ralston, KJ;Hird, SL;Burns, GF
T细胞整联蛋白LFA-1在细胞间接触的专门区域的聚集启动整联蛋白介导的粘附和下游信号传导，这些事件是成功的免疫应答所必需的。但如何实现和维持集群尚不清楚。在这里，我们建立了一个LFA-1相关的分子，PTA-1，是本地化的膜筏，并结合肌动蛋白结合蛋白4.1G的异构体的羧基末端结构域。已知蛋白4.1与膜相关鸟苷酸激酶同源物（人类椎间盘大）相关。我们发现，PTA-1的羧基末端肽也可以结合人类的光盘大，这种肽的存在或不存在极大地影响PTA-1和不同亚型的4.1G之间的结合。用佛波酯或PTA-1交联的T细胞刺激诱导PTA-1和4.1G与细胞骨架紧密结合，并且来自这种活化细胞的PTA-1现在可以结合到4.1G的氨基末端区域。我们建议，这些动态协会提供了一个受管制的分子粘附复合物，用于集群和运输LFA-1和相关分子的结构基础。
Clustering of the T cell integrin, LFA-1, at specialized regions of intercellular contact initiates integrin-mediated adhesion and downstream signaling, events that are necessary for a successful immunological response. But how clustering is achieved and sustained is not known. Here we establish that an LFA-1-associated molecule, PTA-1, is localized to membrane rafts and binds the carboxyl-terminal domain of isoforms of the actin-binding protein 4.1G. Protein 4.1 is known to associate with the membrane-associated guanylate kinase homologue, human discs large. We show that the carboxyl-terminal peptide of PTA-1 also can bind human discs large and that the presence or absence of this peptide greatly influences binding between PTA-1 and different isoforms of 4.1G. T cell stimulation with phorbol ester or PTA-1 cross-linking induces PTA-1 and 4.1G to associate tightly with the cytoskeleton, and the PTA-1 from such activated cells now can bind to the amino-terminal region of 4.1G. We propose that these dynamic associations provide the structural basis for a regulated molecular adhesive complex that serves to cluster and transport LFA-1 and associated molecules.