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利用蛋白酪氨酸激酶抑制剂剖析T细胞抗原受体信号传导

Dissection of T cell antigen receptor signaling using protein tyrosine kinase inhibitors.

作者信息

Baldari C T, Telford J L

机构信息

Department of Evolutionary Biology, University of Siena, Italy.

出版信息

Eur J Immunol. 1994 May;24(5):1046-52. doi: 10.1002/eji.1830240506.

DOI:10.1002/eji.1830240506
PMID:8181516
Abstract

T cell antigen receptor (TcR) recognition of appropriately presented antigen results in the rapid activation of protein tyrosine kinases. Subsequent events include activation of protein kinase C and increased intracellular free calcium which lead to the activation of transcription factors involved in regulating interleukin-2 gene expression. We have assayed the ability of a panel of protein tyrosine kinase (PTK) inhibitors to interfere with activation of the NF-AT transcription factor by TcR ligation or treatment with phorbol ester and calcium ionophore which bypass many of the early events of TcR signal transduction. The results indicate that PTK are involved in early and late stages of TcR signaling. Moreover, one inhibitor (genistein) revealed the existence of a PTK which down-regulates specifically calcium-mediated signaling at a point downstream of the PTK p56lck but upstream of calcium mobilization.

摘要

T细胞抗原受体(TcR)对适当呈递的抗原的识别导致蛋白酪氨酸激酶的快速激活。随后的事件包括蛋白激酶C的激活和细胞内游离钙的增加,这导致参与调节白细胞介素-2基因表达的转录因子的激活。我们检测了一组蛋白酪氨酸激酶(PTK)抑制剂通过TcR连接或用佛波酯和钙离子载体处理来干扰NF-AT转录因子激活的能力,佛波酯和钙离子载体绕过了TcR信号转导的许多早期事件。结果表明,PTK参与了TcR信号传导的早期和晚期阶段。此外,一种抑制剂(染料木黄酮)揭示了存在一种PTK,它在PTK p56lck下游但在钙动员上游的一点特异性下调钙介导的信号传导。

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