CD28 IS ASSOCIATED WITH AND INDUCES THE IMMEDIATE TYROSINE PHOSPHORYLATION AND ACTIVATION OF THE TEC FAMILY KINASE ITK/EMT IN THE HUMAN JURKAT LEUKEMIC T-CELL LINE
CD28 IS ASSOCIATED WITH AND INDUCES THE IMMEDIATE TYROSINE PHOSPHORYLATION AND ACTIVATION OF THE TEC FAMILY KINASE ITK/EMT IN THE HUMAN JURKAT LEUKEMIC T-CELL LINE
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DOI：
10.1073/pnas.91.20.9347
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发表时间：
1994-09-27
影响因子：
11.1
通讯作者：
DUPONT, B
中科院分区：
文献类型：
--
作者：
AUGUST, A;GIBSON, S;DUPONT, B
T淋巴细胞需要两种信号才能被激活。抗原特异性T细胞受体可以递送第一信号，而通过抗体或其同源配体B7-1（CD 8 O）或B7-2连接T细胞表面分子CD 28已被证明足以递送第二信号。通过CD 28和T细胞受体的信号传导导致（i）它们对T细胞的共刺激以产生包括白细胞介素2的多种淋巴因子和（ii）预防无反应性诱导。除了涉及蛋白酪氨酸磷酸化外，对CD 28介导其信号的途径知之甚少。我们在人类Jurkat细胞中发现，Tec家族蛋白酪氨酸激酶ITK/EMT（p72（ITK/EMT））与CD 28相关，并在CD 28连接后几秒钟内被酪氨酸磷酸化和激活。这种p72的酪氨酸磷酸化（ITK/EMT）是快速的（在30秒内），发生在LCK激活的情况下，并先于鸟嘌呤核苷酸交换因子VAV的酪氨酸磷酸化。CD 28的二次交联对于诱导的p72酪氨酸磷酸化（ITK/EMT）是不必要的。因此，p72的酪氨酸磷酸化（ITK/EMT）可能是CD 28信号转导中最早的事件之一。这表明蛋白酪氨酸激酶的Tec家族的成员，类似于Src和Syk家族的成员，在T细胞的活化中起作用。此外，数据表明，p72（ITK/EMT），并通过类推Tec家族的其他成员，响应于细胞外产生的信号。
T lymphocytes require two signals to be activated. The antigen-specific T-cell receptor can deliver the first signal, while ligation of the T-cell surface molecule CD28 by antibodies or its cognate ligands B7-1 (CD8O) or B7-2 has been demonstrated to be sufficient for the delivery of the second signal. Signaling via CD28 and the T-cell receptor results (i) in their costimulation of T-cells to produce numerous lymphokines including interleukin 2 and (ii) in the prevention of anergy induction. Little is known about the pathway by which CD28 mediates its signals except that protein-tyrosine phosphorylation is involved. We show here in human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT (p72(ITK/EMT)) is associated with CD28 and becomes tyrosine-phosphorylated and activated within seconds of CD28 ligation. This tyrosine phosphorylation of p72(ITK/EMT) is rapid (within 30 sec), occurs in the absence of LCK activation, and precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV. Secondary crosslinking of CD28 is unnecessary for the induced tyrosine phosphorylation of p72(ITK/EMT). Thus, tyrosine phosphorylation of p72(ITK/EMT) may represent one of the earliest events in CD28 signaling. This demonstrates that a member of the Tec family of protein tyrosine kinases, similar to members of the Src and Syk families, plays a role in the activation of T cells. Furthermore, the data demonstrate that p72(ITK/EMT), and by analogy other members of the Tec family, responds to extracellularly generated signals.