Rakesh Kriti, Agrawal Devendra K
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
Biochem Pharmacol. 2005 Sep 1;70(5):649-57. doi: 10.1016/j.bcp.2005.04.042.
Cytokines are secreted proteins that regulate diverse biological functions by binding to receptors at the cell surface to activate complex signal transduction pathways including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Stringent mechanisms of signal attenuation are essential for ensuring an appropriate, controlled cellular response. Three families of proteins, the SH2-containing phosphatases (SHP), the protein inhibitors of activated STATs (PIAS), and the suppressors of cytokine signaling (SOCS), inhibit specific and distinct aspects of cytokine signal transduction. The analysis of mice lacking genes for members of the SHP has shed much light on the roles of these proteins in vivo. In recent in vitro studies, the protein modifiers ubiquitin and small ubiquitin-like modifier (SUMO) have emerged as key players in the strategies employed by SOCS and PIAS to repress signaling. This review throws light on the mechanisms of action of these regulators as being evolved by the latest researches.
细胞因子是分泌蛋白，通过与细胞表面的受体结合来调节多种生物学功能，从而激活包括Janus激酶-信号转导子和转录激活子（JAK-STAT）途径在内的复杂信号转导通路。严格的信号衰减机制对于确保适当、可控的细胞反应至关重要。三类蛋白质，即含SH2结构域的磷酸酶（SHP）、活化STAT蛋白抑制剂（PIAS）和细胞因子信号转导抑制因子（SOCS），抑制细胞因子信号转导的特定且不同的方面。对缺乏SHP家族成员基因的小鼠的分析，极大地揭示了这些蛋白质在体内的作用。在最近的体外研究中，蛋白质修饰剂泛素和小泛素样修饰物（SUMO）已成为SOCS和PIAS用于抑制信号转导策略中的关键参与者。这篇综述通过最新研究揭示了这些调节因子的作用机制。
