Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction

EMBO J. 1993 Jul;12(7):2663-70.

Abstract

Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two cytokines that are secreted by activated T cells and have similar effects on monocytes and B cells. We describe a mutant form of human interleukin-4 (hIL-4) that competitively antagonizes both hIL-4 and human interleukin-13 (hIL-13). The amino acid sequences of IL-4 and IL-13 are approximately 30% homologous and circular dichroism (CD) spectroscopy shows that both proteins have a highly alpha-helical structure. IL-13 competitively inhibited binding of hIL-4 to functional human IL-4 receptors (called hIL-4R) expressed on a cell line which responds to both hIL-4 and IL-13. Binding of hIL-4 to an hIL-4 responsive cell line that does not respond to IL-13, and binding of hIL-4 to cloned IL-4R ligand binding protein expressed on heterologous cells, were not inhibited by IL-13. hIL-4 bound with approximately 100-fold lower affinity to the IL-4R ligand binding protein than to functional IL-4R. The mutant hIL-4 antagonist protein bound to both IL-4R types with the lower affinity. The above results demonstrate that IL-4 and IL-13 share a receptor component that is important for signal transduction. In addition, our data establish that IL-4R is a complex of at least two components one of which is a novel affinity converting subunit that is critical for cellular signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding, Competitive
  • Cell Line
  • Humans
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / metabolism*
  • Interleukins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Oligodeoxyribonucleotides
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin*
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • Receptors, Mitogen / chemistry
  • Receptors, Mitogen / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction*

Substances

  • IL13RA1 protein, human
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukins
  • Oligodeoxyribonucleotides
  • Receptors, Immunologic
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Interleukin-4