Usacheva Anna, Tian Xinyong, Sandoval Raudel, Salvi Debra, Levy David, Colamonici Oscar R
Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
J Immunol. 2003 Sep 15;171(6):2989-94. doi: 10.4049/jimmunol.171.6.2989.
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-alpha 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.
含WD重复序列的活化蛋白激酶C受体（RACK）-1与多种信号系统相关，包括蛋白激酶C、生长因子和干扰素。在干扰素系统中，RACK-1作为衔接蛋白，将转录因子信号转导和转录激活因子1（STAT1）招募至受体复合物。然而，RACK-1在I型干扰素信号传导中应发挥更广泛的作用，因为I型干扰素受体的干扰素α受体2/β亚基中RACK-1结合位点的突变不仅消除了STAT1的激活，还消除了信号转导和转录激活因子2（STAT2）的激活。在本研究中，我们证明RACK-1作为一种支架蛋白，形成一个多蛋白复合物，该复合物包括受体的干扰素α受体2/β链、STAT1、Janus激酶1和酪氨酸激酶2。体外数据进一步表明，在该复合物中，酪氨酸激酶2是负责STAT1磷酸化的酪氨酸激酶。最后，我们提供证据表明，RACK-1也可能作为其他细胞因子系统（如白细胞介素-2、白细胞介素-4和促红细胞生成素）中的支架蛋白。
