Starr R, Hilton D J
Cooperative Research Centre for Cellular Growth Factors, Parkville, Vic., Australia.
Int J Biochem Cell Biol. 1998 Oct;30(10):1081-5. doi: 10.1016/s1357-2725(98)00067-3.
Regulation of many aspects of cell behaviour occurs through the interaction of cytokines with specific cell surface receptors, resulting in the activation of cytoplasmic signal transduction pathways. Although cellular responses to cytokines are tightly controlled, few molecules have been identified which are able to switch these signals off. The suppressors of cytokine signalling (SOCS) proteins are a new family of negative regulators of cytokine signal transduction. SOCS proteins contain a variable amino-terminal region, a central Src-homology 2 (SH2) domain and a novel conserved carboxy-terminal motif termed the SOCS box. The expression of SOCS proteins is induced by cytokine. Once expressed, SOCS downregulate JAK/STAT pathways and hence the biological response. Recent studies, primarily reliant on overexpression of proteins, indicate that SOCS may be involved in modulating additional pathways, suggesting that they may play a more general role in regulating cellular responses to cytokine. The analysis of knockout mice will clarify the physiological role of SOCS in regulating cytokine responsiveness. Mutations leading to the loss of SOCS activity may give rise to cytokine hyperresponsiveness and may contribute to the development of diseases such as diabetes and cancer. Small molecule effectors which modify SOCS function may potentially be useful therapeutics for the treatment of certain diseases.
细胞行为的许多方面是通过细胞因子与特定细胞表面受体的相互作用来调节的，这会导致细胞质信号转导途径的激活。尽管细胞对细胞因子的反应受到严格控制，但能够关闭这些信号的分子却很少被鉴定出来。细胞因子信号转导抑制因子（SOCS）蛋白是细胞因子信号转导的一类新的负调节因子。SOCS蛋白包含一个可变的氨基末端区域、一个中央Src同源2（SH2）结构域和一个称为SOCS框的新型保守羧基末端基序。SOCS蛋白的表达由细胞因子诱导。一旦表达，SOCS就会下调JAK/STAT途径，从而下调生物学反应。最近的研究主要依赖于蛋白质的过表达，表明SOCS可能参与调节其他途径，这表明它们可能在调节细胞对细胞因子的反应中发挥更广泛的作用。对基因敲除小鼠的分析将阐明SOCS在调节细胞因子反应性中的生理作用。导致SOCS活性丧失的突变可能会导致细胞因子超反应性，并可能促成糖尿病和癌症等疾病的发展。修饰SOCS功能的小分子效应物可能潜在地成为治疗某些疾病的有用疗法。
