title: Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin.
abstract: Extracellular proteolysis of thyroglobulin at the apical surface of thyroid epithelial cells results in liberation of thyroxine, and is mediated by lysosomal cysteine proteases such as cathepsins B and L. Here, we report on the expression of the cysteine protease cathepsin K in thyroid epithelial cells. The cDNA for porcine thyroid cathepsin K showed homologies ranging from 71% to 94% to the cDNA of cathepsin K from various species and cell types. The deduced amino acid sequence of porcine thyroid cathepsin K predicted a 37 kDa preproenzyme, with the active site residues Cys-140, His-277 and Asn-297, and one potential N-glycosylation site. The localization of cathepsin K was not restricted to lysosomes. Rather, secreted cathepsin K was predominantly found within the follicular lumen and in association with the apical plasma membrane of thyroid epithelial cells. Enzyme cytochemistry showed that cell-surface associated cathepsin K was proteolytically active at neutral pH. In vitro, recombinant cathepsin K liberated thyroxine from thyroglobulin by limited proteolysis at neutral pH. We postulate that its localization enables cathepsin K to contribute to the extracellular proteolysis of thyroglobulin, i.e. thyroid hormone liberation, at the apical surface of thyroid epithelial cells in situ.
authors.affiliation: Institut für Zellbiologie and Bonner Forum Biomedizin, Rheinische Friedrich-Wilhelms Universität, Ulrich-Haberland-Strasse 61a, D-53121 Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Tepel
authors.forename: D
authors.initials: D
authors.lastname: Brömme
authors.forename: V
authors.initials: V
authors.lastname: Herzog
authors.forename: K
authors.initials: K
authors.lastname: Brix
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018076:DNA, Complementary; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D013954:Thyroglobulin; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534130:CTSK protein, human; D056657:Cathepsin K