The mechanism of IL-5 signal transduction

Am J Physiol. 1998 Sep;275(3):C623-33. doi: 10.1152/ajpcell.1998.275.3.C623.

Abstract

Cytokines are important regulators of hematopoiesis. They exert their actions by binding to specific receptors on the cell surface. Interleukin-5 (IL-5) is a critical cytokine that regulates the growth, activation, and survival of eosinophils. Because eosinophils play a seminal role in the pathogenesis of asthma and allergic diseases, an understanding of the signal transduction mechanism of IL-5 is of paramount importance. 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 shown 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 JAK2 tyrosine kinases and SHP-2 tyrosine phosphatase are important for eosinophil survival. In contrast to their survival-promoting activity, Lyn and JAK2 appear to have no role in eosinophil degranulation or expression of surface adhesion molecules. Raf-1 kinase, on the other hand, is critical for eosinophil degranulation and adhesion molecule expression. Btk is involved in IL-5 stimulation of B cell function. However, it does not appear to be important for eosinophil function. Thus a clear segregation of signaling molecules based on their functional importance is emerging. This review describes the signal transduction mechanism of the IL-3/GM-CSF/IL-5 receptor system and compares and contrasts IL-5 signaling between eosinophils and B cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Eosinophils / physiology
  • Hematopoiesis*
  • Humans
  • Interleukin-5 / physiology*
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Interleukin / chemistry
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-5
  • Signal Transduction / physiology*

Substances

  • Interleukin-5
  • Receptors, Interleukin
  • Receptors, Interleukin-5
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Protein Tyrosine Phosphatases