The plasminogen-like molecule apically secreted by epithelial thyroid cells is sulfated.
Plasminogen (Pl), a circulating protease synthesized in the liver, is also present in several tissues. In the thyroid gland a Pl-like protease was found in the apical lumen where it is involved, through its proteolytic activity, in luminal degradation of thyroglobulin (Tg). Here, we showed for the first time that the Pl-like protease apically secreted by epithelial thyroid cells is sulfated, both on tyrosine residue(s) and on oligosaccharide side chains. The Pl molecule is composed of a large N-terminal moiety made of five distinct Kringle domains (K1-K5) separated by small peptidic fragments, and of a C-terminal domain with serine protease activity. Using a software tool able to predict tyrosine sulfation sites in protein sequences we localized the potential tyrosine sulfation sites of Pl. Then, we became aware that, whatever the species considered, at least three of the four potential tyrosine sulfation sites of Pl were located on Kringle sites, and more precisely, for K1, on the highly conserved binding domain of K1. We determined with the same software tool which potential sulfation sites were the most likely to be really sulfated. We hypothesize that the sulfation of these sites modulates the binding properties of Pl.
Giraud
Annie
A
INSERM U555, Faculté de Médecine, Université de la Méditerranée, 27 Bd. Jean Moulin, 13385 Marseille Cedex 5, France. Annie.Giraud@medecine.univ-mrs.fr
Chabaud
Odile
O
Lejeune
Pierre-Jean
PJ
Barbaria
Jocelyne
J
Mallet
Bernard
B
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016764:Cell Polarity; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D013552:Swine; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D009844:Oligosaccharides; D013431:Sulfates; D014443:Tyrosine; D010958:Plasminogen; D013954:Thyroglobulin