Schistosoma mansoni TGF-beta receptor II: role in host ligand-induced regulation of a schistosome target gene

PLoS Pathog. 2006 Jun;2(6):e54. doi: 10.1371/journal.ppat.0020054. Epub 2006 Jun 16.

Abstract

Members of transforming growth factor-beta (TGF-beta) superfamily play pivotal roles in development in multicellular organisms. We report the functional characterization of the Schistosoma mansoni type II receptor (SmTbetaRII). Mining of the S. mansoni expressed sequence tag (EST) database identified an EST clone that shows homology to the kinase domain of type II receptors from different species. The amplified EST sequence was used as a probe to isolate a cDNA clone spanning the entire coding region of a type II serine/threonine kinase receptor. The interaction of SmTbetaRII with SmTbetaRI was elucidated and shown to be dependent on TGF-beta ligand binding. Furthermore, in the presence of human TGF-beta1, SmTbetaRII was able to activate SmTbetaRI, which in turn activated SmSmad2 and promoted its interaction with SmSmad4, proving the transfer of the signal from the receptor complex to the Smad proteins. Gynaecophoral canal protein (GCP), whose expression in male worms is limited to the gynaecophoric canal, was identified as a potential TGF-beta target gene in schistosomes. Knocking down the expression of SmTbetaRII using short interfering RNA molecules (siRNA) resulted in a concomitant reduction in the expression of GCP. These data provide evidence for the direct involvement of SmTbetaRII in mediating TGF-beta-induced activation of the TGF-beta target gene, SmGCP, within schistosome parasites. The results also provide additional evidence for a role for the TGF-beta signaling pathway in male-induced female reproductive development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / physiology
  • Animals
  • Cloning, Molecular
  • DNA, Complementary
  • Drug Interactions
  • Female
  • Gene Expression Regulation
  • Genome
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Host-Parasite Interactions
  • Humans
  • Larva
  • Ligands
  • Male
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Receptors, Transforming Growth Factor beta / physiology*
  • Schistosoma mansoni / growth & development
  • Schistosoma mansoni / metabolism*

Substances

  • DNA, Complementary
  • Helminth Proteins
  • Ligands
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II