Characterization of the Ras homologue of Schistosoma mansoni

Ahmed Osman, Edward G. Niles, Philip T. Loverde

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Ras is a member of a super-family of guanine-binding or G-proteins. Ras functions as a molecular switch in the transduction of signals generated by the activation of a variety of cell surface receptors and relays the signals to downstream effectors. Little is known about signal transduction in schistosomes. In order for Schistosoma mansoni to survive different immune responses triggered by the host as well as to migrate from the site of penetration at the skin to the final destination in portal circulation, they must receive signals from the host environment and respond to them in a way that allows their survival. We have isolated the schistosome Ras cDNA by using sequence information of the schistosome Ras homologue submitted to the Genbank database. Analysis of the encoded peptide revealed 81% identity and 92% similarity with K-Ras from various species. Ras is a single copy gene as determined by quantitative hybridization experiments. The cDNA was cloned into pGEX-4T and the expressed peptide was used to generate specific antibody reagents. Affinity purified antibodies identified a 23 kDa native protein that localizes to the subtegument. Ras is not associated with the tegument. Ras is expressed in all the developmental stages of the parasite. However, Ras is over-expressed in female worms compared to males. Schistosome Ras was also shown to be post-translationally modified by addition of farnesyl isoprenoid moiety to the cysteine residue in the C-terminal box. Using a schistosome extract in vitro SmRas farnesylation was inhibited by the farnesyl transferase inhibitor, FTI-277, at concentrations comparable to those required to inhibit K-Ras processing. These initial studies on signal transduction in schistosomes should provide a solid basis for improving our understanding of schistosome-host interactions. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)27-41
Number of pages15
JournalMolecular and Biochemical Parasitology
Volume100
Issue number1
DOIs
StatePublished - Apr 15 1999

Keywords

  • Prenylation
  • Ras
  • Schistosoma mansoni
  • Signal transduction

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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