Pseudo-high-affinity IL-2 receptor and growth signal transduction in lymphocytes

We examined whether the psuedo-hlgh-affinity IL-2 receptor (IL-2R)could transduce a growth signal in lymphocytes. Since lymphocytesdevoid of the I chain were not available, we employed functionaldepletion of the I chain from a mouse T cell line CTLL-2 transfectedwith cDNA for the human H chain and its defective mutants whichcan bind IL-2 but cannot transduce a growth signal. The numbersof human H, mouse I, and mouse H chains expressed in these transfectantswere similar to each other. When the human H chain (and mutants)-expressing CTLL-2 transfectants were incubated with 300 pMhuman IL-2, the majority of human H and mouse I chains togetherwith the L chain formed the hlgh-affinity receptor complex whereasthe majority of mouse H chains remained free. When the humanH chain mutant-expressing CTLL-2 transfectants were incubatedwith 300 pM human IL-2, the I chain was expected to be functionallydepleted by the formation of the inactive high-affinity complexwith the inactive human H chain mutants. However, the humanH chain mutant-expressing CTLL-2 transfectants proliferatedwith a half maximal response to human IL-2 at 300–500pM which agrees with the pseudo-high affinity K_d value displayedby the mouse L and H chains. The human H chain-expressing transfectantsproliferated in response the human IL-2 in a similar kineticswith CTLL-2. CTLL-2 and the human H chaln/mutants-transfectantsall responded to mouse IL-2 in the same kinetics. The maximalresponses of each cell line to mouse and human IL-2 were similar.These results suggest that the pseudo-hlgh-affinity IL-2R composedof the L and H chains may transduce a growth signal, and thata molecule other than the I chain may be involved in proliferativesignal transduction.     

IL-9 and its receptor: from signal transduction to tumorigenesis

IL-9 is a multifunctional cytokine secreted by TH2 lymphocytes. Besides its role during immune responses, its growth factor and antiapoptotic activities on multiple transformed cells suggest a potential role in tumorigenesis. Indeed, IL-9 overexpression induces thymic lymphomas in mice, and IL-9 production is associated with Hodgkin disease and HTLV-I transformed T cells in humans. IL-9 activities are mediated by a specific receptor chain that forms a heterodimeric receptor with the common gamma chain also involved in IL-2,4,7,15 and 21 signaling. The IL-9 receptor and common gamma chains associate with JAK1 and JAK3, respectively and trigger the STAT-1, -3 and -5, IRS and RAS-MAPK pathways. Moreover, in vitro, dysregulated IL-9 response can lead to autonomous cell growth and malignant transformation of lymphoid cells associated with constitutive activation of the Jak/STAT pathway.     

T-cell receptor isoforms and signal transduction.

Recent cDNA and genomic cloning have identified CD3 eta as an alternatively spliced product of the same gene locus that encodes CD3 zeta. Three distinct T-cell receptor isoforms have now been identified. A current view of the signal transduction function of these isoforms in thymocytes and T cells is discussed.     

cAMP对人骨髓瘤细胞的IL-6信号转导功能及细胞增殖的抑制作用

目的 研究ＰＫＡ途径激活（或胞内ｃＡＭＰ水平升高）后对人骨髓瘤细胞的ＩＬ－６信号转导功能及细胞生长的影响。方法 采用ＰＫＡ途径激动剂Ｆｏｓｋｏｌｉｎ（ＦＫ）和ｃＡＭＰ类似物８－Ｂｒ－ｃＡＭＰ刺激人骨髓瘤细胞骨－Ｓｋｏ－００７,分别通过ＭＴＴ方法和凝胶阻滞电泳（ｅｌｅｃｔｒｏｐｈｏｒｅｔｉｃ ｍｏｂｉｌｉｔｙ ｓｈｉｆｔ ａｓｓａｙ,ＥＭＳＡ）方法检测ＦＫ和８－Ｂｒ－ｃＡＭＰ对Ｓｋｏ细胞的生长及其Ｉ     

IL-13Rα2作为功能受体介导信号转导的研究进展

IL-13 is a pleiotropic cytokine mainly secreted by activated Th2 cells. It has 2 receptors, IL-13Rα1 and IL-13Rα2. The latter had been thought to serve exclusively as a decoy receptor for a long period of time due to its short cytoplasmic tail and lack of signal transduction structure. Since Fichtner-Feigl reported in Nature Medicine that IL-13 is involved in induction of TGF-β production and tissue fibrosis through IL-13Rα2-mediated signaling pathway, it was found that IL-13Rα2 has more sophisticated functions than just a simple decoy receptor as more and more researches have explored its signaling functions. This review combines the most advanced research results with previous investigation and discusses the gene structure, expression, production, distribution, subtype conversion and possible signal pathways mediated by this receptor. More importantly, the connection with human diseases and the applications in disease diagnosis and molecule targeted therapy for cancer are also discussed.     

神经调节因子及其信号转导机制

神经调节因子(NRG)是一个由4种基因编码的多肽家族,包含4种同源异构体NRG-1,2,3和4,其功能性受体是由ErbB酪氨酸激酶受体组成,属于跨膜酪氨酸激酶的表皮生长因子受体家族成员,包括ErbB2/HER2/neu,ErbB3/HERS和ErbB4/HER4.NRG通过诱导ErbB受体构象变化,使ErbB蛋白形成二聚体,继而激活酪氨酸激酶,引起C-末端的自身酪氨酸磷酸化和反式酪氨酸磷酸化,而发挥其生物学作用.     

IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts

BACKGROUND: IL-13 and IL-4 share many functional properties as a result of their use of a common receptor complex comprising IL-13 receptor alpha 1 (IL-13Ralpha1) and IL-4 receptor alpha (IL-4Ralpha). The nonsignaling receptor IL-13 receptor alpha 2 (IL-13Ralpha2) binds IL-13 with high affinity and specificity and is believed to be a decoy receptor for IL-13. OBJECTIVE: We sought to examine the inhibitory effects of soluble and membrane-bound IL-13Ralpha2 on IL-13- and IL-4-mediated effects. METHODS: Primary human fibroblasts were grown from endobronchial biopsy specimens obtained from volunteers. Upregulation of IL-13Ralpha2 mRNA was measured by means of RT-PCR, and the level of surface expression was measured by means of FACS. RESULTS: We found that a recombinant soluble form of IL-13Ralpha2 blocked the effects of IL-13, but not IL-4, in fibroblasts in vitro. However, we found that the transmembrane form of IL-13Ralpha2 could attenuate both IL-13 and IL-4 responses, even though the response to TNF-alpha was unaffected. Furthermore, we found that IL-13Ralpha2 became associated with IL-4Ralpha in the presence of IL-4. Addition of a blocking antibody to the extracellular domain of IL-13Ralpha2 restored responses of both IL-13 and IL-4. CONCLUSION: The ability of IL-13Ralpha2 to regulate IL-4 was previously unrecognized in primary airway cells. These data reveal a novel role for IL-13Ralpha2 as a negative regulator of both IL-13 and IL-4 signaling in human bronchial fibroblasts. CLINICAL IMPLICATIONS: It appears that IL-13Ralpha2 might be a powerful suppressor of TH2-mediated responses and thus represents a potential therapeutic target for the treatment of asthma.     

IL-6 cytokine family and signal transduction: a model of the cytokine system

The interleukin 6 (IL-6) cytokine family, which includes IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), IL-11 and cardiotrophin-1 (CT-1), exhibits pleiotropy and redundancy in biological activities. The IL-6 family cytokines exhibit a helical structure. Their receptors belong to the type 1 cytokine receptor family. The receptors of the IL-6 family cytokines share a receptor subunit, which explains one of the mechanisms of functional redundancy. In this review, we describe the general features of the IL-6 cytokine family and its signal transduction mechanisms. Many functional properties of the IL-6 family of cytokines and their receptors are general features of the cytokine system.     

LPS受体及其信号传导通路

细菌脂多糖(lipopolysaccharide,LPS)可激活单核细胞、臣噬细胞及内皮细胞,引起细胞因子合成和释放,导致全身性炎症反应发生.而LPS跨膜信号转导是引起细胞效应的关键.本文主要综述与LPS的跨膜信号转导有关Toll样受体一TLR2(Toll-like receptor 2)和(TLR4Toll-like receptor4)的结构特点、配体范围、基因表达调节以及信号转导机制.正是Toll样受体直接将LPS刺激信号传入细胞内,激活NF-κB信号途径,导致效应基因的表达.     

Axoplasmic transport and its signal transduction mechanism

Neuron requires a continual supply of materials synthesized in the cell body, for example a wide range of soluble proteins, membranous components, and various organelles. The transported materials are needed to replace constituents that turn over in the membrane and organelles of the fiber and also are needed to bring substances participating in energy metabolism. Other transported components are neurotransmitters or transmitter-related components supplied to the nerve terminals for the release and subsequent excitation of postsynaptic cells. Moreover, neurotropic substances and modulators are released from the nerve terminals to affect the functional state of the neuron. Conversely, some materials are conveyed back to the cell body. These include organelles, lysosomes, nerve growth factor, and selected small molecules such as adenosine, Ca2+, and some neurotransmitters. Axoplasmic transport is thought to be fundamental for a variety of neuronal cell functions. Thus it may be considered that axoplasmic transport relates to the dynamic physiological activity of neurons; in other words, axoplasmic transport is supposed to express the physiological activity of neurons. In turn, as in the case for many other physiological functions, axoplasmic transport is possibly controlled by neuronal, hormonal, and immunological systems. Since axoplasmic transport supplies neuron materials toward the synapses and back to the cell body, a feedback system of regulatory mechanisms of a variety of neuronal functions might be operated through axoplasmic transport pathways. Although axoplasmic transport is the important neuronal function, its regulation is poorly understood. In this review, we focus on the dynamics of organelle transport and its regulatory mechanisms mediated by neurotransmitters.     

Protein kinase C in IL- 2 signal transduction

Interleukin-2 (IL-2), secreted principally by activated helper T-cells, plays a pivotal role in the generation and regulation of the immune response. The various biologic functions of IL-2 have been the focus of intensive study over the years and have been well worked out. By contrast, an understanding of the intracellular signals coupled to the IL-2 receptor and responsible for mediating IL-2 effects in T-cells is far less developed, and the role that protein kinase C (PKC) may play in the various cellular responses to IL-2 receptor activation is unclear. In this article we will discuss IL-2, its receptors, and IL-2 signal transduction in relation to the physiological roles PKC activation may play in IL-2-mediated activation of T-cells and other hematopoietic cells.     

IL-17/IL-17R信号转导机制及功能的研究进展

IL-17家族包括IL-17A-IL17F 6个成员,其中IL-17A是其原型.作为一种重要的炎症因子,IL-17可诱导多种与炎症相关的趋化因子、炎性细胞因子及抗菌蛋白的产生,在机体的宿主防御中发挥重要作用.然而,大量的研究证实IL-17与多种自身免疫病及炎症疾病密切相关.鉴于IL-17的宿主防御和免疫损伤的双重作用,人们对IL-17/IL-17R信号转导机制及其生理和病理功能进行了更深入的研究,从而为相关疾病的干预和治疗提供了新的思路.     

New insights into T-cell antigen receptor structure and signal transduction.

Recent studies have provided insights into how the complex structure of the T-cell antigen receptor relates to its signal transduction function. Both the CD3 and zeta subunits contain functioning signaling modules that regulate the activation of tyrosine kinases and phosphorylation of cellular substrates.     

巨噬细胞的激活及其信号传导机制的研究进展

巨噬细胞广泛存在于全身各组织,一般处于静息状态,活化以后成为具有活跃生物学功能的效应细胞。巨噬细胞激活的刺激因子主要有细菌、细胞因子、植物血凝素、寄生虫等。巨噬细胞激活的信号传导途径主要有LPS信号传导途径、Ca2 信号传导途径、PKC信号传导途径、JAK-STAT信号传导途径、MAPK信号传导途径、PI3K信号传导途径等。通过不同刺激因子和各种信号传导途径激活的巨噬细胞,构成了可以执行不同免疫功能的复杂群体。