Akiyama S K, Yamada S S, Yamada K M, LaFlamme S E
Laboratory of Developmental Biology, NIDR, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1994 Jun 10;269(23):15961-4.
Integrins are heterodimeric, transmembrane cell adhesion receptors that have recently been shown to function in transmembrane signal transduction. To examine the specific role of integrin intracellular domains in signal transduction, chimeric receptors containing various integrin intracellular domains coupled to a reporter consisting of the transmembrane and extracellular domains of the small, non-signaling subunit of the interleukin-2 receptor were expressed in cultured human fibroblasts and assayed for their ability to trigger tyrosine phosphorylation of the 125-kDa cytoplasmic tyrosine kinase, pp125FAK. Tyrosine phosphorylation of pp125FAK was induced in cultured fibroblasts that transiently expressed chimeric receptors containing either the beta 1, beta 3, or beta 5 integrin intracellular domain and were selected by magnetic bead sorting. However, expression of chimeric receptors containing either the alpha 5 or an alternatively spliced form of the beta 3 intracellular domain (beta 3B), as well as those lacking an intracellular domain, failed to induce tyrosine phosphorylation of pp125FAK. These results indicate that information contained in the beta 1, beta 3, or beta 5 integrin intracellular domain is sufficient to stimulate integrin-mediated tyrosine phosphorylation of specific intracellular proteins and that integrin extracellular and transmembrane domains are not required for inducing tyrosine phosphorylation. Our results also indicate that alternative splicing can regulate the ability of beta integrin intracellular domains to participate in signal transduction, and they further suggest that the carboxyl-terminal region of specific beta integrins may play a role in the signal transduction pathway involving extracellular matrix molecules.
整合素是异二聚体跨膜细胞黏附受体，最近研究表明其在跨膜信号转导中发挥作用。为了研究整合素细胞内结构域在信号转导中的具体作用，将含有各种整合素细胞内结构域的嵌合受体与由白细胞介素-2受体小的无信号亚基的跨膜和细胞外结构域组成的报告基因偶联，在培养的人成纤维细胞中表达，并检测其触发125-kDa细胞质酪氨酸激酶pp125FAK酪氨酸磷酸化的能力。在瞬时表达含有β1、β3或β5整合素细胞内结构域的嵌合受体并通过磁珠分选筛选的培养成纤维细胞中，诱导了pp125FAK的酪氨酸磷酸化。然而，含有α5或β3细胞内结构域的可变剪接形式（β3B）的嵌合受体以及缺乏细胞内结构域的嵌合受体的表达未能诱导pp125FAK的酪氨酸磷酸化。这些结果表明，β1、β3或β5整合素细胞内结构域中包含的信息足以刺激整合素介导的特定细胞内蛋白质的酪氨酸磷酸化，并且诱导酪氨酸磷酸化不需要整合素的细胞外和跨膜结构域。我们的结果还表明，可变剪接可以调节β整合素细胞内结构域参与信号转导的能力，并且进一步表明特定β整合素的羧基末端区域可能在涉及细胞外基质分子的信号转导途径中发挥作用。
