The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi
The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi
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DOI：
10.1074/jbc.274.13.8554
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发表时间：
1999-03-26
影响因子：
4.8
通讯作者：
Linder, ME
中科院分区：
文献类型：
--
作者：
Frazier, WA;Gao, AG;Linder, ME
整合素相关蛋白（IAP; CD47）是一种血小板反应蛋白受体，与β（3）整合素形成信号复合物，导致α（v）β（3）依赖性细胞扩散和趋化性增强，以及血小板中α（IIb）β（3）依赖性扩散和聚集。CD47的这些作用都被百日咳毒素处理的细胞特异性地消除。在这里，我们报道了CD47，它的β（3）整联蛋白伴侣，和G（i）蛋白形成一个稳定的，洗涤剂可溶的复合物，可以通过免疫沉淀和亲和层析回收，G（i α）从这个复合物中释放出来，用GTP或AlF4处理。GTP和AlF4也减少了CD47与其衍生自血小板反应蛋白的激动剂肽（4N1K）的结合，表明CD47与G（i）直接缔合。4N1K肽导致血小板内环AMP水平迅速下降，这是聚集所必需的G（i）依赖性事件。最后，4N1K刺激GTP gamma（35）S与来自表达IAP和alpha（v）beta（3）的细胞的膜的结合。CD47与异源三聚体G蛋白的这种功能性偶联为CD47在多种系统中的生物学效应提供了机制解释。
Integrin-associated protein (IAP; CD47) is a thrombospondin receptor that forms a signaling complex with beta(3) integrins resulting in enhanced alpha(v)beta(3)-dependent cell spreading and chemotaxis and, in platelets, alpha(IIb)beta(3)-dependent spreading and aggregation. These actions of CD47 are all specifically abrogated by pertussis toxin treatment of cells. Here we report that CD47, its beta(3) integrin partner, and G(i) proteins form a stable, detergent-soluble complex that can be recovered by immunoprecipitation and affinity chromatography, G(i alpha) is released from this complex by treatment with GTP or AlF4. GTP and AlF4 also reduce the binding of CD47 to its agonist peptide (4N1K) derived from thrombospondin, indicating a direct association of CD47 with G(i). 4N1K peptide causes a rapid decrease in intraplatelet cyclic AMP levels, a G(i)-dependent event necessary for aggregation. Finally, 4N1K stimulates the binding of GTP gamma(35)S to membranes from cells expressing IAP and alpha(v)beta(3). This functional coupling of CD47 to heterotrimeric G proteins provides a mechanistic explanation for the biological effects of CD47 in a wide variety of systems.