Hagan Suzanne, Garcia Rey, Dhillon Amardeep, Kolch Walter
The Beatson Institute for Cancer Research, Signalling and Proteomics Laboratory, Glasgow, United Kingdom.
Methods Enzymol. 2006;407:248-59. doi: 10.1016/S0076-6879(05)07021-7.
The Raf kinase inhibitor protein (RKIP) belongs to an evolutionarily conserved family of phosphatidylethanolamine-binding proteins (PEBPs), which have important functions as inhibitors of kinase signaling pathways and metastasis. Most notably, RKIP can interrupt signaling through the Ras-Raf-MEK-ERK pathway by dissociating the interaction between Raf-1 and its substrate MEK, highlighting the importance of protein interactions as regulatory interfaces. Furthermore, RKIP was shown to inhibit IkappaB kinases (IKKs) interfering with the activation of nuclear factor kappa B (NFkappaB), and G-protein coupled receptor-kinase 2 (GRK2), impeding receptor downregulation and prolonging signaling. More recently, RKIP has emerged as an important suppressor of metastasis. Here, we review the functions of RKIP and present methods to detect and measure RKIP expression and activity in cells and tissues.
Raf激酶抑制蛋白（RKIP）属于磷脂酰乙醇胺结合蛋白（PEBP）这一进化保守家族，该家族作为激酶信号通路和转移的抑制剂具有重要功能。最值得注意的是，RKIP可通过解离Raf-1与其底物MEK之间的相互作用来中断Ras-Raf-MEK-ERK信号通路，突出了蛋白质相互作用作为调节界面的重要性。此外，RKIP被证明可抑制IκB激酶（IKK），干扰核因子κB（NFκB）的激活，还可抑制G蛋白偶联受体激酶2（GRK2），阻碍受体下调并延长信号传导。最近，RKIP已成为转移的重要抑制因子。在此，我们综述RKIP的功能，并介绍检测和测量细胞及组织中RKIP表达和活性的方法。
