Beadling C, Guschin D, Witthuhn B A, Ziemiecki A, Ihle J N, Kerr I M, Cantrell D A
Lymphocyte Activation Laboratory, London, UK.
EMBO J. 1994 Dec 1;13(23):5605-15. doi: 10.1002/j.1460-2075.1994.tb06898.x.
The activation of Janus protein tyrosine kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins by interleukin (IL)-2, the T cell antigen receptor (TCR) and interferon (IFN) alpha was explored in human peripheral blood-derived T cells and the leukemic T cell line Kit225. An IL-2-induced increase in JAK1 and JAK3, but not JAK2 or Tyk2, tyrosine phosphorylation was observed. In contrast, no induction of tyrosine phosphorylation of JAKs was detected upon stimulation of the TCR. IFN alpha induced the tyrosine phosphorylation of JAK1 and Tyk2, but not JAK2 or JAK3. IFN alpha activated STAT1, STAT2 and STAT3 in T cells, but no detectable activation of these STATs was induced by IL-2. However, IL-2 regulates the DNA binding and tyrosine phosphorylation of two STAT-like protein complexes which do not include STAT1, STAT2 or STAT3. STAT4 is not activated by IL-2. The activation of STAT5 cannot be excluded, so the IL-2-activated complexes most probably include at least one novel STAT. No STAT activity was detected in TCR-stimulated lymphocytes, indicating that the JAK/STAT pathway defined in this study constitutes an IL-2R-mediated signaling event which is not shared by the TCR. Finally, in other cell types the correlation between JAK1 activation and the induction of STAT1 has suggested that JAK1 may activate STAT1. The observation that IL-2 and IFN alpha activate JAK1 to a comparable degree, but only IFN alpha activates STAT1, indicates that JAK1 activation is not the only determining factor for STAT1 activation. Moreover, the data show that JAK1 stimulation is also not sufficient for STAT3 activation.
在人外周血来源的T细胞和白血病T细胞系Kit225中，研究了白细胞介素（IL）-2、T细胞抗原受体（TCR）和干扰素（IFN）α对Janus蛋白酪氨酸激酶（JAKs）以及信号转导和转录激活因子（STAT）蛋白的激活作用。观察到IL-2诱导JAK1和JAK3的酪氨酸磷酸化增加，但JAK2或Tyk2未出现这种情况。相比之下，刺激TCR后未检测到JAKs酪氨酸磷酸化的诱导。IFNα诱导JAK1和Tyk2的酪氨酸磷酸化，但JAK2或JAK3未出现这种情况。IFNα激活T细胞中的STAT1、STAT2和STAT3，但IL-2未诱导这些STATs的可检测激活。然而，IL-2调节两种不包括STAT1、STAT2或STAT3的STAT样蛋白复合物的DNA结合和酪氨酸磷酸化。STAT4未被IL-2激活。不能排除STAT5的激活，因此IL-2激活的复合物很可能至少包括一种新的STAT。在TCR刺激的淋巴细胞中未检测到STAT活性，表明本研究中定义的JAK/STAT途径构成了一种IL-2R介导的信号事件，TCR不共享该事件。最后，在其他细胞类型中，JAK1激活与STAT1诱导之间的相关性表明JAK1可能激活STAT1。IL-2和IFNα以相当程度激活JAK1，但只有IFNα激活STAT1，这一观察结果表明JAK1激活不是STAT1激活的唯一决定因素。此外，数据表明JAK1刺激对于STAT3激活也不充分。
