SOCS3与中枢神经再生的研究进展

细胞因子信号转导抑制因子（suppressors of cytokine signaling,SOCS）家族是一类对细胞因子信号通路具有负反馈调节作用的蛋白分子,参与多种细胞因子、生长因子和激素的信号调节。细胞因子对中枢神经系统中的各种生物效应具有广泛多样的调节作用,SOCS家族的许多成员（比如SOCS1,SOCS2和SOCS3等）在发育时期和成年脑内均有表达。近来发现,SOCS3在中枢神经再生中有重要作用。     

001 SOCS:细胞因子信号传导的负反馈抑制因子

细胞因子是一类调节机体免疫和神经内分泌功能的生物活性物质,JAK/STAT通路的激活是细胞因子发挥其生物效应最普遍且最重要的细胞内信号传导通路.细胞因子作用的显著特点是其作用的时间性及空间性均受到严格的调控,至少有3种蛋白质家族参与了其信号传导的负调节,其中以SOCS的研究最深入.本文就SOCS的发现、结构、功能及作用机制做一简要的综述.     

SOCS:细胞因子信号传导的负反馈抑制因子

细胞因子是一类调节机体免疫和神经内分泌功能的生物活性物质 ,JAK/STAT通路的激活是细胞因子发挥其生物效应最普遍且最重要的细胞内信号传导通路。细胞因子作用的显著特点是其作用的时间性及空间性均受到严格的调控 ,至少有 3种蛋白质家族参与了其信号传导的负调节 ,其中以SOCS的研究最深入。本文就SOCS的发现、结构、功能及作用机制做一简要的综述。     

SOCS：细胞因子信号传导的负反馈抑制因子

细胞因子是一类调节机体免疫和神经内分泌功能的生物活性物质，JAK／STAT通路的激活是细胞因子发挥其生物效应最普遍且最重要的细胞内信号传导通路。细胞因子作用的显著特点是其作用的时间性及空间性均受到严格的调控，至少有3种蛋白质家族参与了其信号传导的负调节，其中以SOCS的研究最深入。本文就SOCS的发现，结构，功能及作用机制做一简要的综述。     

信号传导的负性调节因子家族SOCS

细胞因子和相应受体结合 ,引发细胞内信号分子级联反应 ,而SOCS蛋白负性调节细胞因子的JAK STATs信号传导途径 ,且SOCS蛋白作用的直接靶点不同。另一方面STATs可以和SOCS基因的调控序列结合 ,调节SOCS基因的表达。小鼠SOCS基因敲除实验显示 ,该信号负反馈途径有助于调节细胞适度应答。结构上 ,SOCS中间为SH2结构域 ,C 末端是保守的SOCS盒 ,因N 末端差异较大而将SOCS家族分为 5组     

SOOS及其免疫学作用研究进展

SOCS蛋白是细胞因子信号通路重要的抑制剂,最近的研究表明SOCS蛋白是天然免疫和获得性免疫系统中关键的生理性调节剂,它们可以调节树突状细胞的激活和T细胞的发育和分化等活动,并且在免疫性疾病中发挥重要的作用.     

SOCS3与BCR-ABL阴性的骨髓增殖性疾病

一系列细胞因子通过JAK/STAT通路诱导细胞因子信号转导抑制因子(SOCS)基因的表达,SOCS蛋白又负反馈调节细胞因子信号转导通路, 形成细胞因子信号转导反馈调节环。在BCR-ABL阴性的骨髓增殖性疾病的发病机制中,JAK2V617F点突变的发现是一个重大的突破。JAK2V617F点突变可导致SOCS3基因表达的增高,但通过某种机制逃逸了SOCS3的负向调控作用。     

SOCS和IFN对JAK/STAT活化的影响和意义

信号抑制因子(SOCS)是在细胞因子诱导下依赖JAK/STAT通路的信号传导而产生的,继而抑制细胞因子的信号传导,因此SOCS蛋白质被认为可以形成局部经典负反馈回路.IFN是由辅助性T细胞Ⅰ类亚群和自然杀伤细胞等分泌的一种细胞因子,具有多种免疫调节功能.在炎症反应中IFN首先激活JAK,然后再活化与之相结合的STATI和STAT3,从而引起iNOS诱生型一氧化氮表达增强而诱发炎症反应,而IFN在诱导细胞的抗病毒和抗生长反应中也起关键作用.IFN可正向调节SOCS的表达,但是SOCS的过度表达又可以抑制IFN受体的磷酸化及STAT1、STAT3的活化.     

SOCS及其免疫学作用研究进展

SOCS蛋白是细胞因子信号通路重要的抑制剂,最近的研究表明SOCS蛋白是天然免疫和获得性免疫系统中关键的生理性调节剂,它们可以调节树突状细胞的激活和T细胞的发育和分化等活动,并且在免疫性疾病中发挥重要的作用。     

Regulation of the immune system by SOCS family adaptor proteins

Signal transduction via cytokine receptors is regulated by several mechanisms that control initiation, magnitude and duration of the signaling pathways. Cytokine-induced SOCS family adaptors function as feedback inhibitors of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. Specific gene-targeted mice have unveiled critical, non-overlapping functions for SOCS1 and SOCS3 in lymphocyte development and homeostasis, and in the regulation of macrophage and dendritic cell functions. In this review, we will discuss the structure of SOCS proteins, mechanisms by which they control the JAK-STAT pathway and their role in immune regulation.     

Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins

Innate immunity represents the first line of defense against invading pathogens. Toll-like receptors (TLRs) are important for activation of innate immunity. Moreover, cytokines mediate communication of cells and are necessary to mount an appropriately regulated immune response. However, activation of innate immunity has to be tightly controlled to avoid overshooting immune reactions. Suppressor of cytokine signaling (SOCS) proteins have been identified as inducible feedback inhibitors of cytokine receptors and have been shown to be of crucial importance for the limitation of inflammatory responses. In this review, we describe the role of SOCS proteins in macrophages and dendritic cells (DCs). Based on our own findings, we show that SOCS proteins are directly induced by stimulation of TLRs. However, SOCS proteins do not interfere with direct TLR signaling, but avoid overshooting activation by regulating paracrine IFN-beta signaling. In addition, SOCS proteins in macrophages and DCs regulate the sensitivity towards IFN-gamma and GM-CSF, thereby modulating anti-microbial activity of macrophages and differentiation of DCs. We discuss that SOCS induction can also be used by microbes to evade immune defense, and this is exemplified by the parasite Toxoplasma gondii which induces SOCS1 to inhibit IFN-gamma-mediated macrophage activation. Taken together, the findings indicate that SOCS proteins play an important role in the balanced activation of innate immunity during infectious encounter.     

Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins

Summary: The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orchestrate the inflammatory response. The operation of feedback control mechanisms that regulate the duration and the amplitude of antigenic and cytokine receptor signaling is therefore required to prevent hyper-activation of the immune system that could lead to tissue destruction or autoimmunity. Suppressor of cytokine signaling (SOCS) proteins have been identified as a negative feedback loop to cytokine signaling. Recently, the generation of genetically engineered mouse models permitted the evaluation of their function in different processes of the immune responses. In this article, we review new insights into the modular structure of SOCS proteins and the function of SOCS1 and SOCS3 to negatively regulate activation and/or differentiation pathways in macrophages, dendritic cells, and T lymphocytes. Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses.     

Toll-like receptor]

Toll-like receptors (TLRs) have been revealed to recognize specific patterns of microbial components. Recognition of microbial components by TLRs initiates signal transduction pathways, triggering expression of genes, which products control innate immune responses and further instruct development of antigen-specific acquired immunity. TIR domain-containing adaptors, such as MyD88, TIRAP, TRIF, and TRAM, play pivotal roles in TLR signaling pathways. Differential utilization of these TIR domain-containing adaptors provides specificity of individual TLR-mediated signaling pathways. TLR-mediated activation of innate immunity, when in excess, leads to immune disorders such as inflammatory bowel diseases. Therefore, several mechanisms that negatively control TLR signaling pathways and thereby prevent overactivation of innate immunity have been elucidated. Nuclear IkappaB proteins, such as Bcl-3 and IkappaBNS, have been revealed to be responsible for this process, by differentially inhibiting TLR-dependent cytokine production.