The SH3 domain of Tec kinase is essential for its targeting to activated CD28 costimulatory molecule
The SH3 domain of Tec kinase is essential for its targeting to activated CD28 costimulatory molecule
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DOI：
10.1002/eji.200324777
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发表时间：
2004-07-01
影响因子：
5.4
通讯作者：
Nunès, JA
中科院分区：
文献类型：
--
作者：
Garçon, F;Ghiotto, M;Nunès, JA
蛋白酪氨酸激酶的Tec家族在T细胞信号传导中起重要作用。Tec是该激酶家族的原型成员，可以与共刺激分子CD 28相互作用。然而，Tec对CD 28刺激的调节仍然知之甚少。在这里，我们表明，CID 28-B7介导的相互作用可能参与Tec在T细胞和APC之间的接触区的重新定位。在CD 28与特异性抗体或天然配体连接后，Tec易位至质膜，在那里与CD 28分子共定位。Tec的Src同源性3（SH 3）结构域和CD 28的两个富含脯氨酸的基序参与该过程。此外，我们表明，CD 28信号需要的SH 3结构域的Tec以及脯氨酸残基存在于胞质内的CD 28的尾巴。这些结果将为T细胞中Tec激酶的复杂调控提供新的见解。
The Tec family of protein tyrosine kinases plays an important role in T cell signaling. Tec, the prototypical member of this kinase family, can interact with CD28, which is a costimulatory molecule. However, the regulation of Tec upon CD28 stimulation remains poorly understood. Here we show that CID28-B7-mediated interactions are likely involved in the relocalization of Tec at the contact zone between T cells and APC. Upon CD28 ligation with specific antibodies or natural ligands, Tec translocates to the plasma membrane where it colocalizes with the CD28 molecule. The Src-homology 3 (SH3) domain of Tec and the two proline-rich motifs of CD28 are involved in this process. Furthermore, we show that CD28 signaling requires the SH3 domain of Tec as well as proline residues present in the intracytoplasmic tail of CD28. These results should provide new insights into the complex regulation of Tec kinases in T cells.