1995 Volume 115 Issue 8 Pages 570-583
Interleukin-5 (IL-5) regulates the production and function of B cells, eosinophils and basophils. In particular, IL-5 plays a critical role in the development of CD5-positive B (B-1) cells. The pleiotropic activity of IL-5 on target cells is directly dependent on the initial binding to IL-5 specific cell-surface receptor (IL-5R). The IL-5 signals are mediated through the high affinity IL-5R which is composed of two different polypeptide chains, α and β. The α chain is a membrane-penetrated glycoprotein that specifically binds IL-5 and retains features common to the cytokine receptor superfamily. The β chain by itself does not bind IL-5, but it can convert the low affinity IL-5R into the high affinity IL-5R and in indispensable for IL-5 signal transduction. The β chain is shared among receptors for IL-5, IL-3 and GM-CSF and is called βc. The cytoplasmic comains of both IL-5Rα and βc are essential for signal transduction. The membrane proximal proline-rich sequence of the cytoplasmic domain of IL-5Rα was found to be essential for the IL-5-induced proliferative response, expression of nuclear proto-oncogenes such as c-jun, c-fos and c-myc, and activation of Bruton's tyrosine and JAK2 kinases. Furthermore, JAK2 activation correlates with proline residues in Pro-Pro-X-Pro motif in the cytoplasmic domain of IL-5Rα. These results indicate that activation of JAK2 and its substrate is critical to coupling IL-5-induced tyrosine phosphorylation and ultimately mitogenesis. I will discuss about molecular mechanisms of IL-5 signaling and B cell defect in X-linked immunodeficient mice in relation to IL-5 signaling.
