Welte T, Leitenberg D, Dittel B N, al-Ramadi B K, Xie B, Chin Y E, Janeway C A, Bothwell A L, Bottomly K, Fu X Y
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Science. 1999 Jan 8;283(5399):222-5. doi: 10.1126/science.283.5399.222.
The role of STAT (signal transducer and activator of transcription) proteins in T cell receptor (TCR) signaling was analyzed. STAT5 became immediately and transiently phosphorylated on tyrosine 694 in response to TCR stimulation. Expression of the protein tyrosine kinase Lck, a key signaling protein in the TCR complex, activated DNA binding of transfected STAT5A and STAT5B to specific STAT inducible elements. The role of Lck in STAT5 activation was confirmed in a Lck-deficient T cell line in which the activation of STAT5 by TCR stimulation was abolished. Expression of Lck induced specific interaction of STAT5 with the subunits of the TCR, indicating that STAT5 may be directly involved in TCR signaling. Stimulation of T cell clones and primary T cell lines also induced the association of STAT5 with the TCR complex. Inhibition of STAT5 function by expression of a dominant negative mutant STAT5 reduced antigen-stimulated proliferation of T cells. Thus, TCR stimulation appears to directly activate STAT5, which may participate in the regulation of gene transcription and T cell proliferation during immunological responses.
分析了信号转导子和转录激活子（STAT）蛋白在T细胞受体（TCR）信号传导中的作用。响应TCR刺激，STAT5在酪氨酸694位点立即发生短暂磷酸化。蛋白酪氨酸激酶Lck是TCR复合物中的关键信号蛋白，其表达激活了转染的STAT5A和STAT5B与特定STAT诱导元件的DNA结合。Lck在STAT5激活中的作用在Lck缺陷型T细胞系中得到证实，在该细胞系中，TCR刺激诱导的STAT5激活被消除。Lck的表达诱导了STAT5与TCR亚基的特异性相互作用，表明STAT5可能直接参与TCR信号传导。对T细胞克隆和原代T细胞系的刺激也诱导了STAT5与TCR复合物的结合。通过表达显性负性突变体STAT5抑制STAT5功能可降低抗原刺激的T细胞增殖。因此，TCR刺激似乎直接激活STAT5，STAT5可能在免疫反应过程中参与基因转录和T细胞增殖的调节。
