Mukhopadhyay S, Ramars A S, Dash D
Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi -221005, India.
J Cell Biochem. 2001;81(4):659-65. doi: 10.1002/jcb.1088.
Bruton's tyrosine kinase (Btk) plays a crucial role in the maturation and differentiation of B-lymphocytes and immunoglobulin synthesis. Recently Btk has been described to be present in significant amount in human platelets. To investigate the regulation of this kinase in the platelets we studied its subcellular redistribution in the resting and activated cells. In the resting platelets Btk was almost absent from the actin-based cytoskeleton. Upon challenge of the platelet thrombin receptor upto 30% of total Btk appeared in the cytoskeleton and the protein underwent phosphorylation on tyrosine. Translocation of Btk to the cytoskeleton but not aggregation was prevented by cytochalasin B, which inhibits actin polymerization. Wortmannin and genistein (inhibitors of phosphoinositide 3-kinase and protein tyrosine kinase, respectively) decreased while phenylarsine oxide (a tyrosine phosphatase inhibitor) increased the cytoskeletal content of Btk. The association of Btk with the cytoskeleton was regulated by integrin alpha(IIb)beta(3) and partly reversible. Taken together, these data suggest that Btk might be a component of a signaling complex containing specific cytoskeletal proteins in the activated platelets.
布鲁顿酪氨酸激酶（Btk）在B淋巴细胞的成熟与分化以及免疫球蛋白合成过程中发挥着关键作用。最近有研究表明，Btk在人类血小板中大量存在。为了研究该激酶在血小板中的调控机制，我们对其在静息和激活状态细胞中的亚细胞重新分布情况展开了研究。在静息血小板中，基于肌动蛋白的细胞骨架几乎不存在Btk。当血小板凝血酶受体受到刺激时，高达30%的总Btk出现在细胞骨架中，并且该蛋白发生了酪氨酸磷酸化。细胞松弛素B可抑制肌动蛋白聚合，从而阻止Btk向细胞骨架的转位，但不会阻止聚集。渥曼青霉素和金雀异黄素（分别为磷酸肌醇3激酶和蛋白酪氨酸激酶的抑制剂）可降低Btk的细胞骨架含量，而氧化苯胂（一种酪氨酸磷酸酶抑制剂）则会增加其含量。Btk与细胞骨架的结合受整合素α（IIb）β（3）调控，且部分具有可逆性。综上所述，这些数据表明，Btk可能是激活血小板中包含特定细胞骨架蛋白的信号复合物的一个组成部分。
