A CRITICAL CYTOPLASMIC DOMAIN OF THE INTERLEUKIN-5 (IL-5) RECEPTOR-ALPHA CHAIN AND ITS FUNCTION IN IL-5-MEDIATED GROWTH SIGNAL-TRANSDUCTION

Interleukin-5 (IL-5) regulates the production and function of B cells, eosinophils, and basophils. The IL-5 receptor (IL-5R) consists of two distinct membrane proteins, alpha and beta. The alpha chain (IL-5R al pha) is specific to IL-5. The beta chain is the common beta chain (bet a c) of receptors for IL-3 and granulocyte-macrophage colony-stimulati ng factor (GM-CSF). The cytoplasmic domains of both alpha and beta cha ins are essential for signal transduction. In this study, we generated cDNAs of IL-5R alpha having various mutations in their cytoplasmic do mains and examined the function of these mutants by expressing them in IL-3-dependent FDC-P1 cells. The membrane-proximal proline-rich seque nce of the cytoplasmic domain of IL-5R alpha, which is conserved among the or chains of IL-5R, IL-3R, and GM-CSF receptor (GM-CSFR), was fou nd to be essential for the ICS-induced proliferative response, express ion of nuclear proto-oncogenes such as c-jun, c-fos, and c-myc, and ty rosine phosphorylation of cellular proteins including JAK2 protein-tyr osine kinase. In addition, analysis using chimeric receptors,which con sist of the extracellular domain of IL-5R alpha and the cytoplasmic do main of pc suggested that dimerization of the cytoplasmic domain of be ta c may be an important step in activating the IL-5R complex and tran sducing intracellular growth signals.