Differential serine phosphorylation regulates IκB-α inactivation
Differential serine phosphorylation regulates IκB-α inactivation
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DOI：
10.1006/bbrc.1999.0548
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发表时间：
1999-04-21
影响因子：
3.1
通讯作者：
Kerr, LD
中科院分区：
文献类型：
--
作者：
Chen, CL;Yull, FE;Kerr, LD
nf - κ B是一种普遍存在的转录因子，参与免疫反应、急性期反应和病毒感染的信号转导机制。NF-kappa B蛋白通过与一种称为I kappa B的抑制剂结合而保留在细胞质中。对哺乳动物I kappa B- α调控的研究表明，两个氨基末端保守的磷酸丝氨酸是输入信号的靶位点。我们报道禽类I kappa b - α对应的氨基端磷酸丝氨酸是磷酸化的靶点，导致I kappa b - α在刺激下失活。此外，我们还展示了这两个系列的不同角色。丝氨酸40突变为丙氨酸阻断了所有被测试的刺激（tnf - α， phorbol酯，抗cd3和抗cd28），导致nf - κ B活化，而丝氨酸36突变为丙氨酸仅减弱某些转导信号（PMA, tnf - α）。这些新发现支持了禽类I κ B- α氨基端磷酸丝氨酸残基通过不同信号差异介导nf - κ B信号转导通路和激活的假设，从而导致nf - κ B的激活(C) 1999学术出版社。
NF-kappa B is a ubiquitous transcription factor involved in the signal transduction mechanisms of the immune response, acute phase reactions, and viral infections. NF-kappa B proteins are retained in the cytoplasm by association with an inhibitor, termed I kappa B. Studies on the regulation of mammalian I kappa B-alpha have revealed that two amino-terminal conserved phosphoserines are the target sites of incoming signals. We report that the corresponding amino-terminal phosphoserines of avian I kappa B-alpha are phosphorylation targets leading to inactivation of I kappa B-alpha upon stimulation. In addition, we show differential roles for these two serines. Mutation of serine 40 to alanine blocks all stimuli tested (TNF-alpha, phorbol ester, and anti-CD3 and anti-CD28), leading to NF-kappa B activation, while mutation of serine 36 to alanine attenuates only certain transduced signals (PMA, TNF-alpha). These novel findings support the hypothesis that the amino-terminal phosphoserine residues of avian I kappa B-alpha differentially mediate NF-kappa B signal transduction pathways and activation by distinct signals, thereby resulting in the activation NF-kappa B. (C) 1999 Academic Press .