IL-4 Signaling

Interleukin 4 (IL-4) is a cytokine associated with allergy and asthma. The classical IL-4R is predominantly expressed in hematopoietic cells and consists of IL-4Rα and IL-2Rγc. The alternative form of IL-4R is predominantly expressed in non-hematopoietic cells and consists of IL-4R and IL-13Ralpha chains.IL-4 binding to its receptor activates JAK/TYK2 followed by phosphorylation and dimerization of STAT6. The transcriptional regulator STAT6 is able to induce various genes that are involved immune function like IgE and MHC-II. IL-4 induced STAT-6 function can be inhibited by corticosteroids while JAK1 is strongly inhibited by SOCS-1. An alternate pathway involves the IL-4R mediated tyrosyl phosphorylation of IRS-1 followed by activation of the PI3K/AKT/mTOR/p70RSK pathway.