title: Functional identity of receptors for proteolysis-inducing factor on human and murine skeletal muscle.
abstract: BACKGROUND
  Cachexia in both mice and humans is associated with tumour production of a sulphated glycoprotein called proteolysis-inducing factor (PIF). In mice PIF binds with high affinity to a surface receptor in skeletal muscle, but little is known about the human receptor. This study compares the human PIF receptor with the murine.
  
  
  METHODS
  Human PIF was isolated from the G361 melanoma and murine PIF from the MAC16 colon adenocarcinoma. The human PIF receptor was isolated from human skeletal muscle myotubes. Protein synthesis and degradation induced by human and murine PIF was studied in human and murine skeletal muscle myotubes.
  
  
  RESULTS
  Both the human and murine PIF receptors showed the same immunoreactivity and Mr 40 000. Both murine and human PIF inhibited total protein synthesis and stimulated protein degradation in human and murine myotubes to about the same extent, and this was attenuated by a rabbit polyclonal antibody to the murine PIF receptor, but not by a non-specific rabbit antibody. Both murine and human PIF increased the activity of the ubiquitin-proteasome pathway in both human and murine myotubes, as evidenced by an increased 'chymotrypsin-like' enzyme activity, protein expression of the 20S and 19S proteasome subunits, and increased expression of the ubiquitin ligases MuRF1 and MAFbx, and this was also attenuated by the anti-mouse PIF receptor antibody.
  
  
  CONCLUSIONS
  These results suggest that the murine and human PIF receptors are identical.
authors.affiliation: Department of Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Mirza
authors.affiliation: Department of Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Tisdale
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D059748:Proteolysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D011509:Proteoglycans; D011956:Receptors, Cell Surface; D025801:Ubiquitin; C042057:proteolysis-inducing peptide; D046988:Proteasome Endopeptidase Complex
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