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白细胞介素-2对信号转导及转录激活因子5（STAT5）的激活需要酪氨酸激酶以及一条不同于Raf1/细胞外信号调节激酶2（ERK2）丝裂原活化蛋白激酶（MAPK）途径的丝氨酸/苏氨酸激酶途径的协同作用。

Interleukin-2 activation of STAT5 requires the convergent action of tyrosine kinases and a serine/threonine kinase pathway distinct from the Raf1/ERK2 MAP kinase pathway.

作者信息

Beadling C, Ng J, Babbage J W, Cantrell D A

机构信息

Lymphocyte Activation Laboratory, Imperial Cancer Research Fund Laboratories, London, UK.

出版信息

EMBO J. 1996 Apr 15;15(8):1902-13.

PMID:8617237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC450109/
Abstract

Interleukin-2 (IL-2) induces DNA binding of STAT5, a member of the family of cytokine-regulated transcription factors termed 'signal transducers and activators of transcription'. IL-2-stimulated STAT5-DNA complexes include two tyrosine phosphoproteins which exhibit distinct mobilities in SDS-PAGE gels. Our studies have shown that IL-2 rapidly induces both tyrosine phosphorylation and serine phosphorylation of STAT5 and that the two STAT5 tyrosine phosphoproteins detected in IL-2-activated cells differ in their levels of phosphorylation on serine residues. The two different phosphoforms of STAT5 have identical in vitro DNA binding specificity and reactivity with tyrosine phosphopeptides, but differ in their cellular localization. As well, the present data indicate that the transcriptional activity of STAT5 is regulated by serine kinases in T lymphocytes. Two previously characterized serine kinases activated by IL-2, MAP kinase/ERK2 and p70 S6 kinase, do not appear to be involved in STAT5 regulation by this cytokine. Accordingly, STAT5 activation in T cells requires the convergent action of tyrosine kinases and a distinct serine/threonine kinase which has not previously been implicated in IL-2 signalling.

摘要

白细胞介素-2（IL-2）可诱导信号转导子和转录激活子（STAT）5的DNA结合，STAT5是细胞因子调节转录因子家族的成员。IL-2刺激的STAT5-DNA复合物包含两种酪氨酸磷酸化蛋白，它们在SDS-PAGE凝胶中表现出不同的迁移率。我们的研究表明，IL-2可迅速诱导STAT5的酪氨酸磷酸化和丝氨酸磷酸化，并且在IL-2激活的细胞中检测到的两种STAT5酪氨酸磷酸化蛋白在丝氨酸残基的磷酸化水平上有所不同。STAT5的两种不同磷酸化形式在体外具有相同的DNA结合特异性和与酪氨酸磷酸肽的反应性，但在细胞定位上有所不同。此外，目前的数据表明，STAT5的转录活性在T淋巴细胞中受丝氨酸激酶调节。两种先前已被鉴定为由IL-2激活的丝氨酸激酶，即丝裂原活化蛋白激酶/细胞外信号调节激酶2（MAPK/ERK2）和p70核糖体蛋白S6激酶，似乎不参与该细胞因子对STAT5的调节。因此，T细胞中STAT5的激活需要酪氨酸激酶和一种以前未涉及IL-2信号传导的独特丝氨酸/苏氨酸激酶的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/8208b13d5624/emboj00008-0160-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/518c26a999df/emboj00008-0154-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/152f0a1a5e94/emboj00008-0155-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/1a30bf84b77d/emboj00008-0155-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/07db77f201dc/emboj00008-0156-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/356f9d90dee0/emboj00008-0156-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/6da74ebbf762/emboj00008-0158-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/c25f3b535fbb/emboj00008-0158-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/8208b13d5624/emboj00008-0160-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/518c26a999df/emboj00008-0154-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/152f0a1a5e94/emboj00008-0155-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/1a30bf84b77d/emboj00008-0155-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/07db77f201dc/emboj00008-0156-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/356f9d90dee0/emboj00008-0156-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/6da74ebbf762/emboj00008-0158-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/c25f3b535fbb/emboj00008-0158-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ee/450109/8208b13d5624/emboj00008-0160-a.jpg

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