Zhang J G, Farley A, Nicholson S E, Willson T A, Zugaro L M, Simpson R J, Moritz R L, Cary D, Richardson R, Hausmann G, Kile B T, Kent S B, Alexander W S, Metcalf D, Hilton D J, Nicola N A, Baca M
Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, Victoria 3050, Australia.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2071-6. doi: 10.1073/pnas.96.5.2071.
The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors. These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.
细胞因子信号转导抑制蛋白（SOCS）家族作为几种细胞因子信号转导途径的细胞内抑制剂发挥作用。它们的表达由Janus激酶/信号转导子和转录激活子（JAK/STAT）途径的细胞因子激活诱导，并且它们通过随后直接与活化的JAK或受体相互作用来抑制JAK/STAT途径，从而作为负反馈环发挥作用。这些相互作用至少部分由SOCS蛋白的SH2结构域介导，但这些蛋白还包含一个高度保守的C末端同源结构域，称为SOCS框。在此我们表明，SOCS框介导与延伸蛋白B和C的相互作用，这反过来可能将SOCS蛋白及其底物与蛋白酶体蛋白降解途径偶联起来。类似于含F盒蛋白家族，似乎SOCS蛋白可能作为衔接分子，将活化的细胞信号蛋白靶向到蛋白降解途径。
