Hilton D J, Richardson R T, Alexander W S, Viney E M, Willson T A, Sprigg N S, Starr R, Nicholson S E, Metcalf D, Nicola N A
The Walter and Eliza Hall Institute for Medical Research and The Cooperative Research Center for Cellular Growth Factors, Parkville, Victoria 3050, Australia.
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):114-9. doi: 10.1073/pnas.95.1.114.
The four members of the recently identified suppressor of cytokines signaling family (SOCS-1, SOCS-2, SOCS-3, and CIS, where CIS is cytokine-inducible SH2-containing protein) appear, by various means, to negatively regulate cytokine signal transduction. Structurally, the SOCS proteins are composed of an N-terminal region of variable length and amino acid composition, a central SH2 domain, and a previously unrecognized C-terminal motif that we have called the SOCS box. By using the SOCS box amino acid sequence consensus, we have searched DNA databases and have identified a further 16 proteins that contain this motif. These proteins fall into five classes based on the protein motifs found N-terminal of the SOCS box. In addition to four new SOCS proteins (SOCS-4 to SOCS-7) containing an SH2 domain and a SOCS box, we describe three new families of proteins that contain either WD-40 repeats (WSB-1 and -2), SPRY domains (SSB-1 to -3) or ankyrin repeats (ASB-1 to -3) N-terminal of the SOCS box. In addition, we show that a class of small GTPases also contains a SOCS box. The expression of representative members of each class of proteins differs markedly, as does the regulation of expression by cytokines. The function of the WSB, SSB, and ASB protein families remains to be determined.
最近发现的细胞因子信号转导抑制因子家族（SOCS-1、SOCS-2、SOCS-3和CIS，其中CIS是细胞因子诱导含SH2结构域蛋白）的四个成员，似乎通过各种方式对细胞因子信号转导进行负调控。在结构上，SOCS蛋白由长度和氨基酸组成可变的N端区域、一个中央SH2结构域以及一个我们称为SOCS框的此前未被识别的C端基序组成。通过使用SOCS框氨基酸序列共有序列，我们搜索了DNA数据库，并鉴定出另外16种含有该基序的蛋白质。根据在SOCS框N端发现的蛋白质基序，这些蛋白质分为五类。除了四种新的含有SH2结构域和SOCS框的SOCS蛋白（SOCS-4至SOCS-7）外，我们还描述了三个新的蛋白质家族，它们在SOCS框的N端分别含有WD-40重复序列（WSB-1和-2）、SPRY结构域（SSB-1至-3）或锚蛋白重复序列（ASB-1至-3）。此外，我们还表明一类小GTP酶也含有SOCS框。每类蛋白质的代表性成员的表达差异显著，细胞因子对其表达的调控也存在差异。WSB、SSB和ASB蛋白家族的功能仍有待确定。
