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. c59 IL-2 stimulates the phosphorylation of ERK2 at Thr 185 and Tyr 187 in thymic blast cells and NKT cells. Stimulation of IL-2 receptor complex with IL-2 induces AKT phosphorylation in CD25+ NKT cells. Stimulation of IL-2 receptor complex with IL-2 induces Gab2 tyrosine phosphorylation in NK3.3 and mycosis fungoides tumor T cells. IL-2 stimulates the phopshorylation of MEK2 at Ser 216 and Ser 222 in thymic blast cells. Stimulation of IL-2 receptor complex with IL-2 induces tyrosine phosphorylation of SHC. Stimulation of IL-2 receptor complex with IL-2 induces phosphorylation of STAT5B in T-cell blasts. Stimulation with IL-2 induces tyrosine phosphorylation of IL-2 receptor gamma chain in T-lymphocytes. Stimulation of IL-2 receptor complex with IL-2 induces Raf1 serine/tyrosine phosphorylation in T-cells which regulates Raf1 kinase activity. IL-2 stimulates the phopshorylation of MEK1 at Ser 218 and Ser 222 in thymic blast cells. Stimulation with IL-2 induces phosphorylation of IL-2 receptor beta subunit at Tyr-364, Tyr-418 and Tyr-536 in YT and HUT-102B2 cells. Stimulation of IL-2 receptor complex with IL-2 induces STAT3 phosphorylation at Tyr-705 and Ser-727 and its activation in peripherial blood T-cells and 3T cell blasts. Stimulation of IL-2 receptor complex with IL-2 induces STAT1 phosphorylation at Tyr-701 and Ser-727 in T cell blasts, T-lymphocytes and Natural killer cells. Stimulation of IL-2 receptor complex with IL-2 induces JAK3 phosphotylation at Tyr-904 and Tyr-939 in T-cells. IL-2 stimulates the phosphorylation of ERK1 at Thr 202 and Tyr 204 in thymic blast cells and NKT cells. Stimulation of IL-2 receptor complex with IL-2 induces tyrosine phosphorylation of SHP2 in F7 and Kit 225 cells. Both A and S regions od IL-2 receptor beta are required for SHP2 phosphorylation. Stimulation of IL-2 receptor complex with IL-2 induces JAK1 phosphorylation in T-cells. Stimulation of IL-2 receptor complex with IL-2 induces phosphorylation of STAT5A at Tyr-694 in T cell blasts. Stimulation of IL-2 receptor complex with IL-2 induces phosphorylation of p85 subunit of PI3K in A49 cells. Stimulation with IL-2 induces the interaction of STAT1 and STAT3 with A domain of IL-2 receptor beta in Kit 225 cells. Stimulation with IL-2 induces the interaction of STAT1 and STAT3 with A domain of IL-2 receptor beta in Kit 225 cells. Type your comment here Stimulation with IL-2 induces the phosphorylation of SYK and its interaction with serine-rich region of IL2RB in human peripheral blood lymphocytes. Stimulation with IL-2 induces phosphorylation of FYN and its interaction with IL-2 receptor beta in COS and mouse pro-B cellline Stimulation of IL-2 receptor complex with IL-2 induces heteromerization of STAT5A and STAT5B and thus leading to their translocation to the nucleus in COS-7 cells and peripherial blood lymphocytes. Stimulation with IL-2 induces phosphorylation of STAT5A on Tyr 694 residue and association of SH2 domains of STAT5 with Tyr-364, Tyr-418 and Tyr-536 residues of IL-2 receptor beta chain Kit 255 cells. Stimulation with IL-2 induces phosphorylation of STAT5B on Tyr 699 residue and its association with IL-2 receptor beta chain Kit 255 cells. Stimulation with IL-2 induces phosphorylation of STAT5A on Tyr 694 residue and association of SH2 domains of STAT5 with Tyr-364, Tyr-418 and Tyr-536 residues of IL-2 receptor beta chain Kit 255 cells. Stimulation with IL-2 induces phosphorylation of STAT5B on Tyr 699 residue and its association with IL-2 receptor beta chain Kit 255 cells. IL-2 stimulates the phosphorylation dependent interaction between GAB2, GRB2, SHP2 and p85 subunit of PI3k in NK3.3 and Kit225 cells. IL-2 stimulates the interaction of CBL with SH3 domain of GRB2 in Kit 225 cells. IL-2 stimulates the interaction of phosphorylated CBL with SH2 domain of p85 subunit of PI3K in Kit 225 cells. IL-2 stimulation leads to a direct physical association of Pyk2 with JAK3 in COS7 cells. SOS recruitment to the cytoplasmic side of the plasma membrane induces the GDP to GTP exchange and activation of RAS. Stimulation of IL-2 receptor complex with IL-2 induces homodimerization of STAT3 in T-lymphocytes and natural killer cells. Stimulation of IL-2 receptor complex with IL-2 induces homomerization of STAT1 in T-lymphocytes and natural killer cells. Stimulation with IL-2 induces the interaction of CISH with A region of IL-2 receptor beta in BaF3 cells. Stimulation of IL-2 receptor complex with IL-2 induces the formation of STAT1 and STAT3 heterodimer in T-lymphocytes and natural killer cells. Stimulation of Il-2 receptor complex leads to the interaction of LCK with P85 subunit of PI3K in HT2 cells. Subsequently, LCK also phosphorylates p85 subunit of PI3K. Stimulation of the IL-2 receptor complex induces the tyrosine phosphorylation of SHC1 and its association with GRB2-SOS1 complex in CTLL2 cells. IL-2 stimulation induces the phosphorylation of Shc and its interaction with IL2RB phosphorylated at Tyr 364 in Kit 225 cells. Activated RAS binds to RAF1 and leads to the activation of RAF1. JAK3 interacts with and phosphorylates IL-2 receptor beta subunit at Tyr-387 through its Box1, Box2 and PQPLXP motifs upon IL-2 stimulation in BaF3 cells. Stimulation of IL-2 receptor complex with IL-2 induces AKT dependent phosphorylation of FOXO3 leading to its rapid inactivation and thereby preventing FOXO3 nuclear translocation in CD4+ T cells. Stimulation of IL-2 receptor complex with IL-2 induces phosphorylation of 40S ribosomal subunit S6 by p70S6 kinase in Kit 225 cells. Stimulation of IL-2 receptor complex induces the phosphorylation of STAT3 by JAK3 in 3T3 cells expressing IL-2 receptor subunits. IL-6 stimulates rapid phosphorylation of SHC1 at Tyr 427 and its interaction with SH2 domain of GRB2 in DeFew-IL-6R/gp130 cells. Stimulation of IL-2 receptor complex induces the phosphorylation and activation of JAK1 which subsequently auguments the phosphorylation of IL-2RB at Tyr 364, Tyr 418 as well as Tyr 536 in COS-1 cells overexpressing JAK1. Stimulation of IL-2 receptor complex by IL-2 stimulation leads to association of Shc1 with IL-2 receptor beta chain via its PTB domain and subsequent tyrosine phosphorylation of Shc1 by JAK1 in 32D cells. Activation of RAF induces the phosphorylation and activation of MEKs Simulation of IL-2 receptor complex induces the phosphorylation and activation of JAK3 which phosphorylate JAK1 in U4A cells. IL-2 stimulates the interaction of GAB2 with SH2 domain of CRKL in Kit-225 cells and T lymphocytes. Stimulation of IL-2 receptor complex with IL-2 induces JAK3 autophosphorylation in COS-7 cells and primary T-lymphocytes. Stimulation of IL- receptor complex with IL-2 induces p70 S6 Kinase phosphorylation in spleenic T-cells Stimulation of IL- receptor complex with IL-2 induces p70 S6 Kinase phosphorylation in spleenic T-cells interleukin-2 signaling pathway PW:0000907 Pathway Ontology Interleukin mediated signaling pathway PW:0000512 Pathway Ontology 20067622 PubMed NetPath: a public resource of curated signal transduction pathways. Genome Biol 2010 Kandasamy K Mohan SS Raju R Keerthikumar S Kumar GS Venugopal AK Telikicherla D Navarro JD Mathivanan S Pecquet C Gollapudi SK Tattikota SG Mohan S Padhukasahasram H Subbannayya Y Goel R Jacob HK Zhong J Sekhar R Nanjappa V Balakrishnan L Subbaiah R Ramachandra YL Rahiman BA Prasad TS Lin JX Houtman JC Desiderio S Renauld JC Constantinescu SN Ohara O Hirano T Kubo M Singh S Khatri P Draghici S Bader GD Sander C Leonard WJ Pandey A