The WD motif-containing protein RACK-1 functions as a scaffold protein within the type IIFN receptor-signalling complex
The WD motif-containing protein RACK-1 functions as a scaffold protein within the type IIFN receptor-signalling complex
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DOI：
10.4049/jimmunol.171.6.2989
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发表时间：
2003-09-15
影响因子：
4.4
通讯作者：
Colamonici, OR
中科院分区：
文献类型：
--
作者：
Usacheva, A;Tian, XY;Colamonici, OR
含有WD重复序列的蛋白受体活化蛋白激酶C(RACK)-1与多种信号系统相连，包括蛋白激酶C、生长因子和干扰素。在干扰素系统中，Rack-1作为一个适配器将转录因子STAT1招募到受体复合体。然而，Rack-1应该在I型干扰素信号转导中发挥更广泛的作用，因为I型干扰素受体2/β亚基中Rack-1结合位点的突变不仅会取消STAT1，还会取消STAT2的激活。在这项研究中，我们证明了Rack-1作为多蛋白复合体的支架蛋白，该复合体包括干扰素-a受体2/受体的β链、STAT1、Janus激酶1和酪氨酸激酶2。体外数据进一步表明，在这个复合体中，酪氨酸激酶2负责STAT1的磷酸化。最后，我们提供了证据，Rack-1也可以作为其他细胞因子系统的支架蛋白，如IL-2，IL-4和促红细胞生成素。《免疫学杂志》，2003年。
The WD repeat-containing protein receptor for activated protein kinase C (RACK)-1 has been linked to a variety of signaling systems including protein kinase C, growth factors, and IFNs. In the IFN system, RACK-1 functions as an adaptor recruiting the transcription factor STAT1 to the receptor complex. However, RACK-1 should play a broader role in type I IFN signaling because mutation of the RACK-1 binding site in the IFN-alpha receptor 2/beta subunit of the type I IFN receptor abrogates not only STAT1, but also STAT2, activation. In this study, we demonstrate that RACK-1 serves as a scaffold protein for a multiprotein complex that includes the IFN-a receptor 2/beta-chain of the receptor, STAT1, Janus kinase 1, and tyrosine kinase 2. In vitro data further suggest that within this complex tyrosine kinase 2 is the tyrosine kinase responsible for the phosphorylation of STAT1. Finally, we provide evidence that RACK-1 may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin. The Journal of Immunology, 2003.