Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation.
Proline residues in CD28 and the Src homology (SH)3 domain of Lck are required for T cell costimulation.
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DOI：
10.1084/jem.190.3.375
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发表时间：
1999-08-02
期刊：
影响因子：
--
通讯作者：
Shaw AS
中科院分区：
文献类型：
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作者：
Holdorf AD;Green JM;Levin SD;Denny MF;Straus DB;Link V;Changelian PS;Allen PM;Shaw AS
Src家族酪氨酸激酶Lck和Fyn对于经由T细胞受体的信号传导是关键的。然而，其激活的确切机制尚不清楚。最近Src激酶的晶体结构表明，激酶激活的一个重要机制是通过含脯氨酸序列与Src同源（SH）3结构域的接合。为了验证这一假设，我们鉴定了几种含有潜在SH3配体的T细胞膜蛋白。在这里，我们证明，Lck和Fyn可以激活的脯氨酸基序的CD28和CD2蛋白，分别。支持的作用，LCK在CD28信号，我们表明，CD28信号在转化和原代T细胞需要LCK以及脯氨酸残基的CD28。这些数据表明，Lck在CD 28共刺激中起着至关重要的作用。
The Src family tyrosine kinases Lck and Fyn are critical for signaling via the T cell receptor. However, the exact mechanism of their activation is unknown. Recent crystal structures of Src kinases suggest that an important mechanism of kinase activation is via engagement of the Src homology (SH)3 domain by proline-containing sequences. To test this hypothesis, we identified several T cell membrane proteins that contain potential SH3 ligands. Here we demonstrate that Lck and Fyn can be activated by proline motifs in the CD28 and CD2 proteins, respectively. Supporting a role for Lck in CD28 signaling, we demonstrate that CD28 signaling in both transformed and primary T cells requires Lck as well as proline residues in CD28. These data suggest that Lck plays an essential role in CD28 costimulation.