THE MECHANISM OF IL-5 SIGNAL-TRANSDUCTION

Cytokines are important regulators of hematopoiesis. They exert their actions by binding to specific receptors on the cell surface. Interleu kin-5 (IL-5) is a critical cytokine that regulates the growth, activat ion, and survival of eosinophils. Because eosinophils play a seminal r ole in the pathogenesis of asthma and allergic diseases, an understand ing of the signal transduction mechanism of IL-5 is of paramount impor tance. The IL-5 receptor is a heterodimer of alpha- and beta-subunits. The alpha-subunit is specific, whereas the beta-subunit is common to IL-3, IL-5, and granulocyte/ macrophage colony-stimulating factor (GM- CSF) receptors and is crucial for signal transduction. It has been sho wn that there are two major signaling pathways of IL-5 in eosinophils. IL-5 activates Lyn, Syk, and JAK2 and propagates signals through the Ras-MAPK and JAK-STAT pathways. Studies suggest that Lyn, Syk, and JAK 2 tyrosine kinases and SHP-2 tyrosine phosphatase are important for eo sinophil survival. In contrast to their survival-promoting activity, L yn and JAK2 appear to have no role in eosinophil degranulation or expr ession of surface adhesion molecules. Raf-l kinase, on the other hand, is critical for eosinophil degranulation and adhesion molecule expres sion. Btk is involved in IL-5 stimulation of B cell function. However, it does not appear to be important for eosinophil function. Thus a cl ear segregation of signaling molecules based on their functional impor tance is emerging. This review describes the signal transduction mecha nism of the IL-3/GM-CSF/IL-5 receptor system and compares and contrast s IL-5 signaling between eosinophils and B cells.