Interleukin 5 (IL-5) ligand belongs to the cytokine superfamily. IL-5 is a glycoprotein which belongs to the cytokine superfamily. It possesses the four helical bundle motifs that is conserved among several hematopoietic cytokines. IL-5 plays an important role in the proliferation and differentiation of eosinophils. IL-5 induces terminal maturation of eosinophils, prolongs eosinophils survival by delaying apoptotic death, increases eosinophils adhesion to endothelial cells and enhances eosinophils effector function (1, 2). IL-5 plays important roles in the pathogenesis of asthma, hypereosinophilic syndromes and eosinophil-dependent inflammatory diseases (3, 4, 5, 6). IL-5 is produced by eosinophils, mast cells, Th2 cells, Tc2 cells and gamma delta T cells (7, 8). IL-5 exerts influence on different biological activities by associating with the IL-5 receptor. This receptor is a heterodimeric complex consisting of an alpha chain-IL5RA and a beta chain, CSF2RB, which is shared between IL-5 receptor, IL-3 receptor and granulocyte macrophage colony stimulating factor receptor (9, 10, 11, 12).

Binding of IL-5 to the receptor complex results in the recruitment of adapter proteins including SHC1 (13), GRB2 (14) and SOS1. This leads to the activation of the Ras/Raf/MEK/ERK cascade (15, 16, 17). Subsequent activation of transcription factors including JUN and ELK-1 regulates the expression of genes involved in the control of cell growth and differentiation. IL-5 stimulation also resulted in the activation of PI3K/AKT/RPS6K pathway resulting in the phosphorylation of RPS6 and regulation of gene expression (17, 18, 19, 20, 21). JAK phosphorylation and activation is also brought about by IL-5, which in turn results in the activation and nuclear translocation of STAT proteins (22, 23, 24, 25). The STAT transcription factors are responsible for the expression of early response genes and feedback inhibitor of JAK/STAT pathway. In addition, IL-5 is known to activate various tyrosine kinases such as LYN (22, 26, 27), BTK (18, 28) and SYK (18, 27). The interactions and intersections between canonical and non-canonical IL-5 signaling systems are depicted in the pathway map.

References

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