Serine phosphorylation of biosynthetic pro‐urokinase from human tumor cells

FEBS Letters

Migliaccio, Antimo¹  Blasi, Francesco²  Stoppelli, M.Patrizia²  Auricchio, Ferdinando¹  Mastronicola, M.Rosaria² 

[1] Institute of General Pathology, 1st Medical School, Naples, Italy;International Institute of Genetics and Biophysics, CNR, via Marconi 10, 80125 Naples, Italy

关键词: Plasminogen activator;    Phosphoserine;    Metastasis;    Secretion;   

DOI  :  10.1016/0014-5793(90)81519-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown