STAT1, JAK2, STAT4, IL-23, PDK (PDPK1), PI3K cat class IA, STAT5, SOCS3, IL-17F, AKT(PKB), RelA (p65 NF-kB subunit), IL23R, PtdIns(3,4,5)P3, IL-23 receptor, STAT3, I-kB, PtdIns(4,5)P2, 18.104.22.168, PI3K reg class IA, NF-kB1 (p50), IL-12RB1, Tyk2, IL-17, ROR-gamma
IL23 signaling pathway
Interleukin-23 ( IL-23 ) plays important role in expanding and maintaining the Th17 cell population, a novel T-cell subset involved in antimicrobial immune response and establishment of many autoimmune diseases .
Interleukin-23 receptor ( IL-23 receptor ) is composed of Interleukin-12 receptor beta-1 ( IL-12RB1 ) chain and Interleukin 23 alpha subunit p19 ( IL23A ). IL23A associates with Janus kinase 2 ( Jak2 ) and in a ligand-dependent manner with Signal transducer and activator of transcription STAT3 . IL-12RB1 interacts directly with Tyrosine kinase 2 ( Tyk2 ) .
IL-23 induced activation of STAT3 leads to direct binding of phosphorylated STAT3 to Interleukin-17 ( IL-17 ) and Interleukin 17F ( IL-17F ) promoters . STAT3 up-regulates the expression of Retinoic Acid Receptor-Related Orphan Receptor Gamma-T ( ROR-gamma ), a Th17 specific transcriptional regulator that is critical for the expression of two members of Interleukin-17 family, IL-17A ( IL-17 ) and IL-17F , , .
IL-23 induced JAK2 activation triggers Phosphoinositide-3-kinase ( PI3K )/ RAC-alpha serine/threonine kinase ( AKT ) and Nuclear factor kappaB ( NF-kB ) pathways which are required for IL-17 production. PI3K/ AKT pathway is involved in STAT3 phosphorylation through an undetermined mechanism .
V-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) ( RelA (p65 NF-kB subunit) ) and Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) ( NF-kB1 (p50) ) bind IL17 promoter and up-regulate its expression .
Suppressor of cytokine signaling 3 ( SOCS3 ) may inhibit JAK2 activity, thereby decreasing IL-23 induced IL-17 and IL-17F expression .