Urokinase-type plasminogen activator up-regulates the expression of its cellular receptor

The expression of the receptor for the urokinase-type plasminogen activator (uPAR) can be regulated by several hormones, cytokines, tumor promoters, e tc. Recently, it has been reported that uPAR is capable of transducing sign als, el en though it is lacking a transmembrane domain and a cytoplasmatic tail. We now report that uPAR cell surface expression can be positively reg ulated by its ligand, uPA, in thyroid cells. The effect of uPA is independe nt of its proteolytic activity, since inactivated uPA or its aminoterminal fragment hare the same effects of the active enzyme. The increase of uPAR o n the cell surface correlates with an increase of specific uPAR mRNA. Final ly, uPA up-regulates uPAR expression also in other cell lines of different type and origin, thus suggesting that the regulatory role of uPA on uPAR ex pression is not restricted to thyroid cells, but it occurs in different tis sues, both normal and tumoral. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.