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IL-2 signaling pathway

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IL-2 is a multifunctional cytokine with pleiotropic effects on several cells of the immune system. IL-2 was originally discovered as a T cell growth factor, but it was also found to have actions related to B cell proliferation, and cytolytic activity of natural killer cells. IL-2 also activates lymphokine activated killer cells. In contrast to its proliferative effects, IL-2 also has potent activity in a process known as activation-induced cell death. More recently, IL-2 was shown to promote tolerance through its effects on regulatory T cell development. IL-2 clinically has anti-cancer effects as well as utility in supporting T cell numbers in HIV/AIDS. There are three classes of IL-2 receptors, binding IL-2 with low, intermediate, or high-affinity. The low affinity receptor (IL-2Rα alone) is not functional; signaling by IL-2 involves either the high affinity hetero-trimeric receptor containing IL-2Rα, IL-2Rβ and the common cytokine receptor gamma chain (originally named IL-2Rγ and now generally denoted as γc) or the intermediate affinity heterodimeric receptor composed of IL-2Rβ and γc. IL-2 stimulation induces the activation of the Janus family tyrosine kinases JAK1 and JAK3, which associate with IL-2Rβ and γc, respectively. These kinases in turn phosphorylate IL-2Rβ and induce tyrosine phosphorylation of STATs (signal transducers and activators of transcription) and various other downstream targets. The downstream signaling pathways activated by IL-2 also involves mitogen-activated protein kinase and phosphoinositide 3-kinase signaling modules, leading to both mitogenic and anti-apoptotic signals. Please access this pathway at [http://www.netpath.org/netslim/IL_2_pathway.html NetSlim] database. NetPath is a collaborative project between PandeyLab at Johns Hopkins University (http://pandeylab.igm.jhmi.edu) and the Institute of Bioinformatics (http://www.ibioinformatics.org). If you use this pathway, please cite the NetPath website until the pathway is published.

IL-2(白介素-2)是一种具有多效性的细胞因子,对免疫系统中的多种细胞产生广泛影响。IL-2最初被发现作为T细胞生长因子,但后来发现其对B细胞增殖和自然杀伤细胞的细胞毒性活性亦具有相关性。此外,IL-2还能激活淋巴因子激活的杀伤细胞。与增殖效应相对,IL-2在激活诱导的细胞死亡过程中亦展现出强大的活性。近期研究表明,IL-2可通过调节T细胞的发育来促进耐受性。在临床应用中,IL-2具有抗肿瘤效应,并能支持HIV/AIDS患者中的T细胞数量。IL-2受体分为三类,分别以低、中、高亲和力与IL-2结合。低亲和力受体(仅IL-2Rα)不具有功能性;IL-2的信号传导涉及高亲和力异三聚体受体(包含IL-2Rα、IL-2Rβ和共同的细胞因子受体γ链,最初命名为IL-2Rγ,现一般称为γc)或中亲和力异二聚体受体(由IL-2Rβ和γc组成)。IL-2的刺激诱导了Janus家族酪氨酸激酶JAK1和JAK3的激活,它们分别与IL-2Rβ和γc结合。这些激酶进而磷酸化IL-2Rβ,并诱导STATs(信号转导子和转录激活子)以及各种其他下游靶点的酪氨酸磷酸化。由IL-2激活的下游信号通路还包括丝裂原活化蛋白激酶和磷脂酰肌醇3激酶信号模块,导致增殖和抗凋亡信号的生成。请访问[http://www.netpath.org/netslim/IL_2_pathway.html NetSlim]数据库以获取此通路信息。NetPath是约翰霍普金斯大学PandeyLab(http://pandeylab.igm.jhmi.edu)和生物信息学研究所(http://www.ibioinformatics.org)之间的合作项目。如使用此通路,请引用NetPath网站,直至通路发表。
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