title: Truncated thioredoxin (Trx80) exerts unique mitogenic cytokine effects via a mechanism independent of thiol oxido-reductase activity.
abstract: Recently we discovered that a naturally occurring C-terminally truncated thioredoxin (Trx80) is a potent mitogenic cytokine stimulating IL-12 production from CD40(+) monocytes. To further characterise Trx80 we have engineered cysteine to serine mutants of Trx80 corresponding to the active site cysteines of Trx (Trx80SGPS) and to the structural cysteine at position 72 (Trx80C72S). Trx80SGPS and Trx80C72S retained the cell stimulatory activity of Trx80 and increased peripheral blood mononuclear cell (PBMC) proliferation three- to five-fold in vitro (P<0.01, n=18). Both Trx80SGPS and Trx80C72S significantly stimulated IL-12 and IFN-gamma secretion from PBMCs in the same manner as Trx80 (P<0.01, n=9 and 10). The previously described Trx80 dimer is caused by non-covalent interactions, and not by any intermolecular disulphide bonds.
authors.affiliation: Medical Nobel Institute for Biochemistry, Department of Biophysics and Biochemistry, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Pekkari
authors.forename: Javier
authors.initials: J
authors.lastname: Avila-Cariño
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Gurunath
authors.forename: Asa
authors.initials: A
authors.lastname: Bengtsson
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
mesh_terms: D001665:Binding Sites; D002455:Cell Division; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008934:Mitogens / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013379:Substrate Specificity; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics
chemical_list: D008934:Mitogens; D010446:Peptide Fragments; C427943:Trx80 protein, human; D018664:Interleukin-12; D013879:Thioredoxins; D007371:Interferon-gamma; D003545:Cysteine