Shaw L M, Turner C E, Mercurio A M
Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 1995 Oct 6;270(40):23648-52. doi: 10.1074/jbc.270.40.23648.
Integrin receptors can mediate transmembrane signaling in response to ligand binding. To further examine the role of the integrin alpha subunit in these signaling functions, we assessed the contribution of the alpha 6 cytoplasmic domain variants to the signaling properties of the alpha 6 beta 1 integrin using P388D1 cells that had been transfected with either the alpha 6A or the alpha 6B cDNA. The alpha 6A beta 1 and alpha 6B beta 1 receptors induced marked quantitative differences in the tyrosine phosphorylation of several proteins after binding to laminin. Specifically, the alpha 6A cytoplasmic domain was more effective than the alpha 6B cytoplasmic domain in inducing the tyrosine phosphorylation of three major proteins (molecular mass, 120, 110, and 76 kDa). In addition to these proteins, we also observed that the tyrosine phosphorylation of the cytoskeletal protein paxillin was increased significantly more by alpha 6A beta 1 integrin-mediated adhesion to laminin than by that of alpha 6B beta 1. This differential pattern of tyrosine phosphorylation induction does not appear to be a secondary event initiated by cell shape changes. Also, differences in tyrosine phosphorylation in the alpha 6 transfectants were not evident in response to attachment to other substrates. These findings provide biochemical evidence for functional differences between alpha subunit cytoplasmic domain variants of the same integrin.
整合素受体可响应配体结合介导跨膜信号传导。为了进一步研究整合素α亚基在这些信号传导功能中的作用，我们使用已转染α6A或α6B cDNA的P388D1细胞，评估了α6胞质结构域变体对α6β1整合素信号传导特性的贡献。α6Aβ1和α6Bβ1受体在与层粘连蛋白结合后，诱导几种蛋白质的酪氨酸磷酸化出现明显的定量差异。具体而言，α6A胞质结构域在诱导三种主要蛋白质（分子量分别为120、110和76 kDa）的酪氨酸磷酸化方面比α6B胞质结构域更有效。除了这些蛋白质外，我们还观察到，与α6Bβ1整合素介导的与层粘连蛋白的粘附相比，α6Aβ1整合素介导的与层粘连蛋白的粘附使细胞骨架蛋白桩蛋白的酪氨酸磷酸化显著增加。这种酪氨酸磷酸化诱导的差异模式似乎不是由细胞形状变化引发的次级事件。此外，α6转染细胞中酪氨酸磷酸化的差异在对附着于其他底物的反应中并不明显。这些发现为同一整合素的α亚基胞质结构域变体之间的功能差异提供了生化证据。
