Interleukin-12 signaling

IL12 is involved in the differentiation of naive T cells into Th1 cells and sometimes known as T cell-stimulating factor. IL12 enhances the cytotoxic activity of Natural Killer cells and CD8+ cytotoxic T lymphocytes. IL12 also has anti-angiogenic activity, mediated by increased production of CXCL10 via interferon gamma.

The IL12 receptor is a heterodimer formed by Interleukin-12 receptor subunit beta-1 (IL12RB1) and Interleukin-12 receptor subunit beta-2 (IL12RB2), both of which have extensive homology to IL6ST (gp130), the signal transducing receptor subunit of the IL6-like cytokine superfamily. IL-12RB2 is considered to play the key role in IL12 function, in part because its expression on activated T cells is stimulated by cytokines that promote Th1 cell development and inhibited by those that promote Th2 cells development. In addition, IL12 binding leads to IL12RB2 tyrosine phosphorylation, which provides binding sites for the kinases Non-receptor tyrosine-protein kinase TYK2 and Tyrosine-protein kinase JAK2. These activate transcription factor proteins in the Signal transducer and activator of transcription (STAT) family, particularly STAT4.