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Serine phosphorylation of biosynthetic pro‐urokinase from human tumor cells
Author(s) -
Mastronicola M.Rosaria,
Stoppelli M.Patrizia,
Migliaccio Antimo,
Auricchio Ferdinando,
Blasi Francesco
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)81519-t
Subject(s) - phosphorylation , zymogen , serine , phosphorylation cascade , biochemistry , extracellular , intracellular , proteolysis , microbiology and biotechnology , chemistry , activator (genetics) , protein phosphorylation , plasmin , biology , enzyme , gene , protein kinase a
Phosphorylation is a potent mechanism regulating the activity of many intracellular enzymes. We have discovered that the product of the human urokinase plasminogen activator gene, pro‐uPA, is phosphorylated in serine in at least two human cell lines. Phosphorylation occurs within the cell during biosynthesis, and phosphorylated intracellular pro‐uPA is secreted into the medium. Of the secreted pro‐uPA molecules, 20–50% are phosphorylated in serine, thus representing a meaningful fraction of the total biosynthetic pro‐uPA. Although the sites of phosphorylation have not yet been determined, at least two such sites must exist; in fact plasmin cleavage of phosphorylated single chain pro‐uPA yields a two chain uPA in which both chains are phosphorylated. A specific function for pro‐uPA phosphorylation has not yet been identified; however, it is tempting to speculate that, as in many other cases, phosphorylation may affect the activity of the enzyme, its response to inhibitors or the conversion of pro‐uPA zymogen to active two‐chain uPA. This would represent an additional way of regulating extracellular proteolysis, an important pathway involved in both intra‐ and extravascular phenomena like fibrinolysis, cell migration and invasiveness.