title: Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release.
abstract: Ferritin is an iron-storage protein that exists in both intracellular and extracellular compartments. We have previously identified H-kininogen (high-molecular-weight kininogen) as a ferritin-binding protein [Torti and Torti (1998) J. Biol. Chem. 273, 13630-13635]. H-Kininogen is a precursor of the potent pro-inflammatory peptide bradykinin, which is released from H-kininogen following cleavage of H-kininogen by the serine protease kallikrein. In this report, we demonstrate that binding of ferritin to H-kininogen occurs via the modified light chain of H-kininogen, and that ferritin binds preferentially to activated H-kininogen. We further demonstrate that binding of ferritin to H-kininogen retards the proteolytic cleavage of H-kininogen by kallikrein and its subsequent release of bradykinin from H-kininogen. Ferritin does not interfere with the ability of kallikrein to digest a synthetic substrate, suggesting that ferritin specifically impedes the ability of kallikrein to digest H-kininogen, perhaps by steric hindrance. Based on these results, we propose a model of sequential H-kininogen cleavage and ferritin binding. These results are consistent with the hypothesis that the binding of ferritin to H-kininogen may serve to modulate bradykinin release.
authors.affiliation: Department of Cancer Biology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Parthasarathy
authors.forename: Suzy V
authors.initials: SV
authors.lastname: Torti
authors.forename: Frank M
authors.initials: FM
authors.lastname: Torti
mesh_terms: D001920:Bradykinin / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000378:metabolism*; D019679:Kininogen, High-Molecular-Weight / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding
chemical_list: D019679:Kininogen, High-Molecular-Weight; D005293:Ferritins; D007610:Kallikreins; D001920:Bradykinin