A TRANSCRIPTION FACTOR WITH SH2 AND SH3 DOMAINS IS DIRECTLY ACTIVATED BY AN INTERFERON-ALPHA-INDUCED CYTOPLASMIC PROTEIN TYROSINE KINASE(S)
A TRANSCRIPTION FACTOR WITH SH2 AND SH3 DOMAINS IS DIRECTLY ACTIVATED BY AN INTERFERON-ALPHA-INDUCED CYTOPLASMIC PROTEIN TYROSINE KINASE(S)
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DOI：
10.1016/0092-8674(92)90106-m
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发表时间：
1992-07-24
期刊：
影响因子：
64.5
通讯作者：
FU, XY
中科院分区：
文献类型：
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作者：
FU, XY
干扰素刺激基因因子3(ISGF3)是干扰素-α诱导的主要转录因子，由113、91、84和48kd四种蛋白质组成。本文报道了ISGF3的113、91和84kd(ISGF3-α)蛋白含有保守的SH2和SH3结构域。特异性干扰素α诱导的胞浆蛋白酪氨酸激酶(S)可以与ISGF3-α蛋白形成一过性复合体。只有在干扰素-α治疗后，这些ISGF3-α蛋白才能被抗磷酸酪氨酸抗体免疫沉淀。P-32标记的ISGF3-α蛋白的磷酸氨基酸分析证实，ISGF3-α蛋白在体外和体内都是干扰素-α反应中直接酪氨酸磷酸化的蛋白，这种酪氨酸磷酸化可以被星形孢子素和金雀异黄素抑制。磷酸酶处理这些ISGF3-α蛋白会在体外抑制ISGF3复合体的形成。这些观察表明，干扰素α诱导ISGF3-α蛋白的直接酪氨酸磷酸化是激活转录因子ISGF3所必需的。
Interferon-stimulated gene factor 3 (ISGF3), the primary transcription factor induced by interferon-alpha, is a complex of four (113, 91, 84, and 48 kd) proteins. This paper reports that the 113, 91, and 84 kd (ISGF3-alpha) proteins of ISGF3 contain conserved SH2 and SH3 domains. A specific interferon alpha-induced cytoplasmic protein tyrosine kinase(s) can form a transient complex with ISGF3-alpha proteins. These ISGF3-alpha proteins can be immunoprecipitated by anti-phosphotyrosine antibodies only after interferon-alpha treatment. Phosphoamino acid analyses of P-32-labeled ISGF3-alpha proteins confirm that ISGF3-alpha proteins are directly tyrosine phosphorylated both in vitro and in vivo in response to interferon-alpha, and this tyrosine phosphorylation can be inhibited by staurosporine and genistein. Phosphatase treatment of these ISGF3-alpha proteins results in inhibition of ISGF3 complex formation in vitro. These observations indicate that interferon alpha-induced direct tyrosine phosphorylation of ISGF3-alpha proteins is necessary for activation of the transcription factor ISGF3.