IL-2 signaling pathway

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是一种具有多功能的细胞因子，对免疫系统中的多种细胞具有多效性影响。IL-2最初被发现作为T细胞的生长因子，但后来发现其作用与B细胞的增殖以及自然杀伤细胞的细胞毒性活性相关。IL-2还能够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也表现出强大的活性。近期研究表明，IL-2通过调节性T细胞发育的影响，能够促进耐受性。在临床应用中，IL-2具有抗肿瘤效应，并且有助于支持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；IL-2的信号传导涉及高亲和力异源三聚体受体，该受体包含IL-2Rα、IL-2Rβ以及共同的细胞因子受体γ链（最初命名为IL-2Rγ，现通常表示为γc），或由IL-2Rβ和γc组成的中间亲和力异源二聚体受体。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。这些激酶随后磷酸化IL-2Rβ，并诱导STATs（信号转导子和转录激活因子）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涉及丝裂原活化蛋白激酶和磷脂酰肌醇3激酶信号模块，导致既有促有丝分裂又有抗凋亡信号。请访问[http://www.netpath.org/netslim/IL_2_pathway.html NetSlim]数据库获取此通路信息。NetPath是由约翰霍普金斯大学的PandeyLab（http://pandeylab.igm.jhmi.edu）和生物信息学研究所（http://www.ibioinformatics.org）共同发起的合作项目。若使用此通路，请在通路发表前引用NetPath网站。