Hamazaki Y, Kojima H, Mano H, Nagata Y, Todokoro K, Abe T, Nagasawa T
Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Oncogene. 1998 May 28;16(21):2773-9. doi: 10.1038/sj.onc.1201799.
Tec is a non-receptor type tyrosine kinase which is tyrosine phosphorylated and activated upon stimulation of hematopoietic cells with various cytokines. The role of Tec in G protein-coupled receptor- and integrin-mediated signalings has not been elucidated. We therefore investigated the regulation of Tec in human blood platelets. Tec was rapidly tyrosine phosphorylated in response to platelet agonists which activate G protein-coupled receptors such as thromboxane A2 analog (U46619), thrombin, and thrombin receptor activating peptide (TRAP). TRAP-induced phosphorylation in Tec was significantly reduced under the conditions which abrogate fibrinogen binding to GP IIb-IIIa and subsequent platelet aggregation. However, TRAP induced significant levels of the phosphorylation even under these conditions and also in thrombasthenic platelets which lack functional GP IIb-IIIa molecules, suggesting that activation of G-protein-coupled receptor causes the phosphorylation. To clarify whether integrin engagement by itself causes the phosphorylation in Tec, we examined the state of the phosphorylation in platelets activated by integrin engagement. Platelet adhesion to immobilized fibrinogen or collagen induced significant levels of the phosphorylation. Furthermore, Tec was translocated to cytoskeleton in response to TRAP in a manner dependent on platelet aggregation, suggesting that Tec can be a component of integrin-mediated signalings. These results collectively indicate that Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets.
Tec是一种非受体型酪氨酸激酶，在造血细胞受到多种细胞因子刺激时会发生酪氨酸磷酸化并被激活。Tec在G蛋白偶联受体和整合素介导的信号传导中的作用尚未阐明。因此，我们研究了人血小板中Tec的调节情况。Tec会因血小板激动剂（如血栓素A2类似物（U46619）、凝血酶和凝血酶受体激活肽（TRAP））而迅速发生酪氨酸磷酸化，这些激动剂可激活G蛋白偶联受体。在消除纤维蛋白原与GP IIb-IIIa结合及随后血小板聚集的条件下，TRAP诱导的Tec磷酸化显著降低。然而，即使在这些条件下以及在缺乏功能性GP IIb-IIIa分子的血小板无力症血小板中，TRAP仍能诱导显著水平的磷酸化，这表明G蛋白偶联受体的激活会导致磷酸化。为了阐明整合素自身结合是否会导致Tec磷酸化，我们检测了整合素结合激活的血小板中磷酸化状态。血小板与固定化纤维蛋白原或胶原的黏附诱导了显著水平的磷酸化。此外，Tec会以依赖血小板聚集的方式响应TRAP转位至细胞骨架，这表明Tec可能是整合素介导信号传导的一个组成部分。这些结果共同表明，Tec参与了人血小板中G蛋白偶联受体和整合素介导的信号传导。
