Conservation of the genomic structure and receptor-mediated signaling between human and rat IL-24

Genes Immun. 2004 Aug;5(5):363-70. doi: 10.1038/sj.gene.6364101.

Abstract

IL-24/MDA-7 is a new member of the IL-10 family of cytokines, which signals through two heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2). Previously, we identified a rat gene named mob-5, which encodes a secreted protein that shares a high degree of homology with human IL-24. Expression of mob-5 and its putative cell surface receptors was shown to be upregulated by oncogenic ras. Here we show that not only do rat mob-5 and human IL-24 share a strikingly similar genomic structure but also that the rat MOB-5 protein can bind to and signal through the human IL-24 receptors. Like human IL-24, binding of the rat MOB-5 protein to the human IL-24 receptors leads to activation of the JAK/STAT pathway, which in turn supports receptor-dependent survival and proliferation of Ba/F3 cells. Furthermore, using human colon cancer cell lines with somatic knockout of either the mutant or the wild-type k-ras allele, we demonstrate that the human IL-24 receptors also are upregulated by oncogenic ras. Taken together, these results provide strong experimental evidence that MOB-5 is indeed the rat homolog of human IL-24.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Cell Line
  • Cell Proliferation
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Cytokines / pharmacology*
  • Gene Components
  • Gene Expression
  • Genes, Tumor Suppressor
  • Genome, Human
  • Humans
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Interleukins / pharmacology*
  • Molecular Sequence Data
  • Rats
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Signal Transduction
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Cytokines
  • IL24 protein, rat
  • Interleukins
  • Receptors, Interleukin
  • interleukin-20 receptor
  • interleukin-22 receptor
  • interleukin-24
  • ras Proteins