2033 Entrez Gene 6198 Entrez Gene 867 Entrez Gene 1050 Entrez Gene PIK3R2 9655 Entrez Gene MAPK3 JAK1 4790 Entrez Gene NCOA3 NFKBIA 1386 Entrez Gene MAPK1 3635 Entrez Gene Homo sapiens 3667 Entrez Gene IL-4 is a glycoprotein which is composed of 129 amino acids and has a molecular weight of 20kDa. IL-4 and IL-13 are produced by CD4+ cells and exhibit significant functional overlap. Both these cytokines play a critical role in the promotion of allergic responses. IL-4 is primarily involved in promoting the differentiation and proliferation of T helper 2 (TH2) cells and the synthesis of immunoglobulin E (IgE). Apart from its role in allergic responses including asthma, IL-4 was also found to regulate retinal progenitor proliferation, rod photoreceptor differentiation, cholinergic and GABAergic amacrine differentiation and neuroprotection and survival. IL-4 was also found to have regulatory effects in a number of neurological diseases including Alzheimer's disease, Multiple sclerosis, Experimental autoimmune encephelitis. It was also found to relieve inflammatory and neuropathic pain. IL-4 is capable of exerting its biological activities through interaction with two cell surface receptor complexes - Type I IL4 receptor and Type II IL4 Receptor. Both these receptor complexes comprise of a common IL4Rα (CD124) subunit, which is also the functional receptor chain. Type I IL-4 receptor is formed by the interaction of IL4Rα subunit with IL-2γc (CD132). Type II IL-4 receptor is formed by the interaction of IL-4Rα subunit with IL-13Rα. Interaction of IL-4 with its receptor results in receptor dimerization and activation. The Type I receptors activates JAK1 and 3, which are associated with the receptor subunits. The activated JAK phosphorylates tyrosine residues the cytoplasmic tails of the receptor which then serves as docking sites for a number of adaptor or signaling molecules including STAT6. Activated STAT6 dimerizes, translocated to the nucleus and transcriptionally actives genes responsive to IL-4. Many of the key functions of IL4 allergic disorders, including TH2 cell differentiation, airway hyper responsiveness, mucus cell metaplasia and IgE synthesis are dependent on STAT6 activation. Other phosphorylated tyrosine residue bind to proteins with phospho-tyrosine binding (PTB) motifs including IRS proteins. This results in the phosphorylation of the IRS proteins, which can then potentially activate the PI3K/AKT cascade by binding to the p85 subunit of PI3K or the Ras/Raf/MEK/ERK cascade. The PI3K/AKT pathway is thought to mediate the growth and survival signals in multiple IL-4 responsive cell types including T- and B- lymphocytes and natural killer cells. (WikiPathways-description) Cellular Process (WikiPathways-category) IL-4 signaling pathway 8660 Entrez Gene 332 Entrez Gene 5595 Entrez Gene 6772 Entrez Gene 5777 Entrez Gene STAT6 SOCS1 2625 Entrez Gene 2353 Entrez Gene 7297 Entrez Gene 5970 Entrez Gene MAPK14 SOS1 1051 Entrez Gene 6778 Entrez Gene 3717 Entrez Gene 6464 Entrez Gene 8262 Entrez Gene GRB2 2242 Entrez Gene PRKCZ 3551 Entrez Gene 4792 Entrez Gene IL4R BIRC5 5295 Entrez Gene STAT5A Entrez Gene JAK3 9046 Entrez Gene SHC1 5600 Entrez Gene GAB2 ELK1 STAT5B NFIL3 PIK3CA IL-4 induces the interaction of PIK3CD,PIK3CA with PIK3R1,PIK3R2 in human neutrophils. PIK3CD JAK2 SOCS3 3269 Entrez Gene 4783 Entrez Gene 5781 Entrez Gene AKT1 MAPK1 MAPK11 HRH1 IL-4 induces the formation of a complex consisting of IL-4 receptor alpha and common gamma chain. IL2RG STAT1 FES STAT3 EP300 NFKB1 CEBPB STAT6 STAT1 STAT5A IKBKB RPS6KB1 STAT3 NFKB1 MAPK3 STAT5B DOK2 IL-4 stimulation leads to tyrosine phosphorylation of DOK2 and subsequent interaction of DOK2 with N-terminal SH2 domain of RASA1 in 32D cells. RASA1 INPP5D CHUK STAT5A 9021 Entrez Gene IL4 1147 Entrez Gene STAT6 207 Entrez Gene ATF2 6778 Entrez Gene 6654 Entrez Gene 3566 Entrez Gene 6774 Entrez Gene STAT6 CEBPA IRS2 STAT6 CBL 5594 Entrez Gene 2885 Entrez Gene FOS 5290 Entrez Gene PTPN11 3718 Entrez Gene 5293 Entrez Gene IRS1 RELA 5296 Entrez Gene PIK3R1 572 Entrez Gene PTPN6 1432 Entrez Gene 8651 Entrez Gene STAT6 9846 Entrez Gene SOCS5 BAD GATA3 TYK2 3565 Entrez Gene 2002 Entrez Gene RELA 3561 Entrez Gene STAT5B Entrez Gene 3716 Entrez Gene