T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and their association with Lck.
T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and their association with Lck.
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T 细胞受体结合诱导 FAK 和 Pyk2 的酪氨酸磷酸化及其与 Lck 的关联。
DOI：
10.4049/jimmunol.159.4.1753
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发表时间：
1997
影响因子：
4.4
通讯作者：
H. Ostergaard
中科院分区：
文献类型：
--
作者：
N. N. Berg;H. Ostergaard
已知通过TCR的刺激诱导许多蛋白质的酪氨酸磷酸化，这导致T细胞的功能活化。鉴定磷酸化的底物并确定它们与其他信号分子的相互作用将为控制T细胞活化的机制提供深入了解。粘着斑激酶（FAK）和最近描述的Pyk 2激酶是非受体蛋白酪氨酸激酶家族的同源成员。FAK已被证明在TCR刺激后变得磷酸化，但其在T细胞活化中的作用（如果有的话）仍有待确定。虽然Pyk 2已显示在通过G蛋白偶联受体刺激的神经元细胞活化中起作用，但尚未描述在T细胞活化中的作用。在这项研究中，我们表明，FAK和Pyk 2是两个主要的115- 120-kDa的蛋白质，成为酪氨酸磷酸化的T细胞后TCR复合物刺激。此外，与酪氨酸磷酸化的增加相一致，我们显示了这些激酶与酪氨酸激酶Lck的SH 2结构域在体内的关联。然而，FAK和Pyk 2的酪氨酸磷酸化的增加发生在Lck缺陷细胞中，这表明这两种激酶的磷酸化不需要Lck。综上所述，这些结果表明FAK和Pyk 2可能与Lck协同作用，在T细胞活化中发挥作用。
Stimulation through the TCR is known to induce tyrosine phosphorylation of a number of proteins, which leads to functional activation of T cells. Identification of the substrates that become phosphorylated and defining their interactions with other signaling molecules will provide insight into the mechanisms controlling T cell activation. Focal adhesion kinase (FAK) and the recently described Pyk2 kinase are homologous members of a non-receptor protein tyrosine kinase family. FAK has been shown to become phosphorylated upon TCR stimulation, but its role, if any, in T cell activation remains to be defined. Although Pyk2 has been shown to play a role in neuronal cell activation stimulated through G-protein-coupled receptors, a role in T cell activation has not been described. In this study we show that FAK and Pyk2 are two of the major 115-to-120-kDa proteins that become tyrosine phosphorylated in T cells following TCR complex stimulation. Furthermore, coincident with the increase in tyrosine phosphorylation, we show an association of these kinases with the SH2 domain of the tyrosine kinase Lck in vivo. The increase in tyrosine phosphorylation of both FAK and Pyk2, however, occurs in Lck-deficient cells suggesting that phosphorylation of both of these kinases does not require Lck. Taken together, these results suggest that FAK and Pyk2, perhaps in coordination with Lck, play a role in T cell activation.