Blystone S D, Lindberg F P, LaFlamme S E, Brown E J
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Cell Biol. 1995 Aug;130(3):745-54. doi: 10.1083/jcb.130.3.745.
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.
利用K562细胞转染模型，我们先前已经描述了整合素αvβ3和α5β1之间的一种新关系。αvβ3的连接能够抑制α5β1介导的吞噬作用，而对α5β1介导的黏附没有影响。αvβ3依赖性抑制显然需要一个信号转导级联反应，因为它被丝氨酸/苏氨酸激酶抑制剂逆转。现在，我们研究了该系统中的信号转导机制，发现β3胞质尾对于启动导致α5β1吞噬作用抑制的信号既是必要的也是充分的。整合素相关蛋白（IAP）的连接与αvβ3信号转导有关，只有当存在具有完整胞质尾的β3整合素时，它才模拟αvβ3连接的作用。虽然纤连蛋白介导的吞噬作用需要α5β1的高亲和力构象，但αvβ3/IAP的连接并不阻止这种高亲和力状态的获得。我们得出结论，αvβ3/IAP连接启动了一个依赖于β3胞质尾的信号转导级联反应，该反应在整合素亲和力调节后的一个步骤中抑制α5β1的吞噬功能。
