Miron S, Kachalsky S G, Hershkoviz R, Lider O
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
J Leukoc Biol. 1997 Sep;62(3):405-13. doi: 10.1002/jlb.62.3.405.
The initial stages of T cell activation involve tyrosine protein kinase-mediated intracellular signaling events. Integrin-mediated adhesion of CD4+ T lymphocytes to extracellular matrix glycoproteins, such as fibronectin, is an activation-dependent process. The involvement of tyrosine protein kinases in the adhesion of CD4+ T cells to fibronectin was examined using pervanadate, a protein-tyrosine phosphatase inhibitor. Pervanadate induced the adhesion of human CD4+ T cells to immobilized fibronectin in a beta1 integrin-mediated fashion, and adhesion was associated with an increase of protein tyrosine phosphorylation. Tyrosine protein kinase inhibitors abrogated both T cell adhesion and intracellular protein tyrosine phosphorylation. Participation of cytoskeletal proteins in the pervanadate-induced T cell adhesion was indicated because cytoskeleton disruption by cytochalasin B inhibited cell adhesion to fibronectin. We demonstrate that the cytoskeletal protein paxillin underwent time-dependent tyrosine phosphorylation simultaneously with pervanadate-induced T cell adhesion to fibronectin. Tyrosine phosphorylation of paxillin was related to cell adhesion, since pretreatment of T cells with cytochalasin B abrogated both adhesion and phosphorylation. This study demonstrates a correlation between activation of protein tyrosine kinases, tyrosine phosphorylation of paxillin, and integrin-mediated T cell adhesion to extracellular matrix glycoproteins.
T细胞活化的初始阶段涉及酪氨酸蛋白激酶介导的细胞内信号转导事件。整合素介导的CD4+ T淋巴细胞与细胞外基质糖蛋白（如纤连蛋白）的黏附是一个依赖于活化的过程。使用偏钒酸盐（一种蛋白酪氨酸磷酸酶抑制剂）研究了酪氨酸蛋白激酶在CD4+ T细胞与纤连蛋白黏附中的作用。偏钒酸盐以β1整合素介导的方式诱导人CD4+ T细胞与固定化纤连蛋白的黏附，且黏附与蛋白酪氨酸磷酸化的增加相关。酪氨酸蛋白激酶抑制剂消除了T细胞黏附和细胞内蛋白酪氨酸磷酸化。细胞骨架蛋白参与了偏钒酸盐诱导的T细胞黏附，因为细胞松弛素B破坏细胞骨架抑制了细胞与纤连蛋白的黏附。我们证明，细胞骨架蛋白桩蛋白与偏钒酸盐诱导的T细胞与纤连蛋白的黏附同时发生时间依赖性酪氨酸磷酸化。桩蛋白的酪氨酸磷酸化与细胞黏附相关，因为用细胞松弛素B预处理T细胞可消除黏附和磷酸化。本研究证明了蛋白酪氨酸激酶的活化、桩蛋白的酪氨酸磷酸化以及整合素介导的T细胞与细胞外基质糖蛋白的黏附之间的相关性。
