'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent kinases in macrophages
'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent kinases in macrophages
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DOI：
10.1038/ni1548
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发表时间：
2008-02-01
影响因子：
30.5
通讯作者：
Ivashkiv, Lionel B.
中科院分区：
文献类型：
--
作者：
Wang, Lu;Tassiulas, Ioannis;Ivashkiv, Lionel B.
基于免疫受体酪氨酸的活化基序（ITAM）偶联受体调节巨噬细胞对Toll样受体和细胞因子受体刺激反应的幅度和性质。然而，使这种受体串扰的分子机制是未知的。在这里，我们研究了钙依赖性激酶CaMK和Pyk 2的ITAM相关受体的“下游”的功能，在调节精氨酸诱导的激活的Jak激酶和STAT转录因子。CaMK和Pyk 2传递来自整合素和含ITAM的衔接子DAP 12的信号，以增强白细胞介素10和干扰素α诱导的Jak活化和STAT 1依赖性基因表达。在系统性红斑狼疮小鼠模型中抑制CaMK抑制STAT 1介导的干扰素-α信号传导我们的研究结果将Pyk 2和Jak激酶与细胞因子和异源ITAM依赖性受体发出的信号联系起来。
Immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors modulate the amplitude and nature of macrophage responses to Toll-like receptor and cytokine receptor stimulation. However, the molecular mechanisms enabling this receptor crosstalk are not known. Here we investigated the function of the calcium-dependent kinases CaMK and Pyk2 'downstream' of ITAM-associated receptors in the regulation of cytokine-induced activation of Jak kinases and STAT transcription factors. CaMK and Pyk2 relayed signals from integrins and the ITAM-containing adaptor DAP12 to augment interleukin 10-and interferon-alpha-induced Jak activation and STAT1-dependent gene expression. CaMK inhibition suppressed STAT1-mediated interferon-alpha signaling in a mouse model of systemic lupus erythematosus. Our results associate Pyk2 and Jak kinases with the linkage of signals emanating from cytokine and heterologous ITAM-dependent receptors.