IL-2 signaling pathway (WP450)

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 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.

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