Integrin beta 3 cytoplasmic tail is necessary and sufficient for regulation of alpha 5 beta 1 phagocytosis by alpha v beta 3 and integrin-associated protein.
Integrin beta 3 cytoplasmic tail is necessary and sufficient for regulation of alpha 5 beta 1 phagocytosis by alpha v beta 3 and integrin-associated protein.
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DOI：
10.1083/jcb.130.3.745
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发表时间：
1995-08
期刊：
影响因子：
--
通讯作者：
Brown EJ
中科院分区：
文献类型：
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作者：
Blystone SD;Lindberg FP;LaFlamme SE;Brown EJ
使用K562细胞转染模型，我们先前已经描述了整合素α v β 3和α 5 β 1之间的新关系。α v β 3连接能够抑制α 5 β 1介导的吞噬作用，而不影响α 5 β 1介导的粘附。α v β 3依赖性抑制显然需要信号转导级联，因为它被丝氨酸/苏氨酸激酶抑制剂逆转。现在，我们已经研究了该系统中的信号转导机制，并发现β 3胞质尾区对于启动导致α 5 β 1吞噬作用抑制的信号既必要又充分。与α v β 3信号转导有关的整联蛋白相关蛋白（IAP）的连接仅在存在具有完整胞质尾区的β 3整联蛋白时才模拟α v β 3连接的作用。尽管纤连蛋白介导的吞噬作用需要α 5 β 1的高亲和力构象，但α v β 3/IAP的连接并不阻止这种高亲和力状态的获得。我们的结论是，α v β 3/IAP连接启动信号转导级联反应，依赖于β 3细胞质尾，抑制α 5 β 1的吞噬功能，在一个步骤后，调节整联蛋白的亲和力。
Using a K562 cell transfection model, we have previously described a novel relationship between the integrins alpha v beta 3 and alpha 5 beta 1. alpha v beta 3 ligation was able to inhibit alpha 5 beta 1- mediated phagocytosis without effect on alpha 5 beta 1-mediated adhesion. The alpha v beta 3-dependent inhibition apparently required a signal transduction cascade as it was reversed by inhibitors of serine/threonine kinases. Now, we have studied the mechanisms of signal transduction in this system and have found that the beta 3 cytoplasmic tail is both necessary and sufficient for initiation of the signal leading to inhibition of alpha 5 beta 1 phagocytosis. Ligation of integrin-associated protein (IAP), which has been implicated in alpha v beta 3 signal transduction, mimics the effects of alpha v beta 3 ligation only when the beta 3 integrin with an intact cytoplasmic tail is present. Although fibronectin-mediated phagocytosis requires the high affinity conformation of alpha 5 beta 1, ligation of alpha v beta 3/IAP does not prevent acquisition of this high affinity state. We conclude that alpha v beta 3/IAP ligation initates a signal transduction cascade, dependent upon the beta 3 cytoplasmic tail, which inhibits the phagocytic function of alpha 5 beta 1 at a step subsequent to modulation of integrin affinity.