[Structure and function of IL-5 receptor].
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, alpha and beta. The alpha chain is a membrane-penetrated glycoprotein that specifically binds IL-5 and retains features common to the cytokine receptor superfamily. The beta 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 beta chain is shared among receptors for IL-5, IL-3 and GM-CSF and is called beta c. The cytoplasmic comains of both IL-5R alpha and beta c are essential for signal transduction. The membrane proximal proline-rich sequence of the cytoplasmic domain of IL-5R alpha 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-5R alpha. 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.
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D004804:Eosinophils / Q000166:cytology; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism / Q000502:physiology; D053614:Janus Kinase 2; D051379:Mice; D008969:Molecular Sequence Data; D011392:Proline; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000502:physiology*; D053649:Receptors, Interleukin-5; D015398:Signal Transduction
D015848:Interleukin-5; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011392:Proline; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2