Upd3--an ancestor of the four-helix bundle cytokines

Biochem Biophys Res Commun. 2013 Jun 21;436(1):66-72. doi: 10.1016/j.bbrc.2013.04.107. Epub 2013 May 22.


The unpaired-like protein 3 (Upd3) is one of the three cytokines of Drosophila melanogaster supposed to activate the JAK/STAT signaling pathway (Janus tyrosine kinases/signal transducer and activator of transcription). This activation occurs via the type-I cytokine receptor domeless, an orthologue of gp130, the common signal transducer of all four-helix bundle interleukin-6 (IL-6) type cytokines. Both receptors are known to exist as preformed dimers in the plasma membrane and initiate the acute-phase response. These facts indicate an evolutionary relation between vertebrate IL-6 and the Drosophila protein Upd3. Here we presented data which strengthen this notion. Upd3 was recombinantly expressed, a renaturation and purification protocol was established which allows to obtain high amounts of biological active protein. This protein is, like human IL-6, a monomeric-α helical cytokine, implicating that Upd3 is an "ancestor" of the four-helix bundle cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytokines / chemistry*
  • Dimerization
  • Disulfides / chemistry
  • Drosophila Proteins / chemistry*
  • Drosophila melanogaster / chemistry*
  • Escherichia coli / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Molecular Sequence Data
  • Protein Sorting Signals
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Signal Transduction


  • Cytokines
  • Disulfides
  • Drosophila Proteins
  • Interleukin-6
  • Protein Sorting Signals
  • Recombinant Proteins
  • Upd3 protein, Drosophila