Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin

Extracellular proteolysis of thyroglobulin at the apical surface of thyroid epithelial cells results in liberation of thyroxine, and is mediated by ly sosomal cysteine proteases such as cathepsins B and L, Here, we report on t he expression of the cysteine protease cathepsin K in thyroid epithelial ce lls. The cDNA for porcine thyroid cathepsin K showed homologies ranging fro m 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 A sn-297, and one potential N-glycosylation site. The localization of catheps in K was not restricted to lysosomes, Rather, secreted cathepsin K was pred ominantly found within the follicular lumen and in association with the api cal plasma membrane of thyroid epithelial cells. Enzyme cytochemistry showe d that cell-surface associated cathepsin K was proteolytically active at ne utral pH, In vitro, recombinant cathepsin K Liberated thyroxine from thyrog lobulin by limited proteolysis at neutral pH, We postulate that its localiz ation enables cathepsin K to contribute to the extracellular proteolysis of thyroglobulin, i.e. thyroid hormone liberation, at the apical surface of t hyroid epithelial cells in situ.