title: Serine phosphorylation of biosynthetic pro-urokinase from human tumor cells.
abstract: 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.
authors.affiliation: International Institute of Genetics and Biophysics, CNR, Naples, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Mastronicola
authors.forename: M P
authors.initials: MP
authors.lastname: Stoppelli
authors.forename: A
authors.initials: A
authors.lastname: Migliaccio
authors.forename: F
authors.initials: F
authors.lastname: Auricchio
authors.forename: F
authors.initials: F
authors.lastname: Blasi
mesh_terms: D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D010768:Phosphoserine / Q000378:metabolism; D011233:Precipitin Tests; D012694:Serine / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; D009363:Neoplasm Proteins; D010768:Phosphoserine; D012694:Serine; D014568:Urokinase-Type Plasminogen Activator