title: Binding of retinoic acid by the inhibitory serpin protein C inhibitor.
abstract: The serpin superfamily includes inhibitors of serine proteases and noninhibitory members with other functions (e.g. the hormone precursor angiotensinogen and the hormone carriers corticosteroid-binding globulin and thyroxine-binding globulin). It is not known whether inhibitory serpins have additional, noninhibitory functions. We studied binding of (3)H-labeled hydrophobic hormones (estradiol, progesterone, testosterone, cortisol, aldosterone, and all-trans-retinoic acid) to the inhibitory serpins antithrombin III, heparin cofactor II, plasminogen activator inhibitor-1, and protein C inhibitor (PCI). All-trans-[(3)H]retinoic acid bound in a specific dose-dependent and time-dependent way to PCI (apparent K(d) = 2.43 microm, 0.8 binding sites per molecule of PCI). We did not observe binding of other hormones to serpins. Intact and protease-cleaved PCI bound retinoic acid equally well, and retinoic acid did not influence inhibition of tissue kallikrein by PCI. Gel filtration confirmed binding of retinoic acid to PCI in purified systems and suggested that PCI may also function as a retinoic acid-binding protein in seminal plasma. Therefore, our present data, together with the fact that PCI is abundantly expressed in tissues requiring retinoic acid for differentiation processes (e.g. the male reproductive tract, epithelia in various organs), suggest an additional biological role for PCI as a retinoic acid-binding and/or delivering serpin.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Jerabek
authors.forename: M
authors.initials: M
authors.lastname: Zechmeister-Machhart
authors.forename: B R
authors.initials: BR
authors.lastname: Binder
authors.forename: M
authors.initials: M
authors.lastname: Geiger
mesh_terms: D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D011485:Protein Binding; D018046:Protein C Inhibitor / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D018046:Protein C Inhibitor; D014212:Tretinoin