A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase.

Abstract

The secretion of plasminogen activators has been implicated in the controlled extracellular proteolysis that accompanies cell migration and tissue remodeling. We found that the human plasminogen activator urokinase (Uk) (Mr 55,000 form) binds rapidly, specifically, and with high affinity to fresh human blood monocytes and to cells of the monocyte line U937. Upon binding, Mr 55,000 Uk was observed to confer high plasminogen activator activity to the cells. Binding of the enzyme did not require a functional catalytic site (located on the B chain of the protein) but did require the noncatalytic A chain of Mr 55,000 Uk, since P/r 33,000 Uk did not bind. These results demonstrate the presence of a membrane receptor for Uk on monocytes and show a hitherto unknown function for the A chain of Uk: binding of secreted enzyme to its receptor results in Uk acting as a membrane protease. This localizes plasminogen activation near the cell surface, an optimal site to facilitate cell migration.

Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in nonalcoholic fatty liver disease

“…11,12 uPAR is expressed by a wide range of immune cells whereas suPAR can be detected in different body fluids, including serum and plasma. [11][12][13][14][15][16][17] Cell-surface uPAR expression is up-regulated upon stimulation with growth factors and cytokines such as interleukin-1β and tumor necrosis factor. 18,19 The full length suPAR shed from the cell surface contains three domains (DI-III), and suPAR can occur in different cleaved forms consisting of only DI or DII-III, with partly divergent biological functions.…”

Stimulation of urokinase-type plasminogen activator receptor expression by PMA requires JNK1-dependent and -independent signaling modules

“…Urokinase can bind speci®cally and with high a nity (K D 90.5 nM) to a 45 ± 60 kDa heavily glycosylated cell surface receptor (u-PAR) (Stoppelli et al, 1986;Vassalli et al, 1985). The receptor is comprised of three similar repeats approximately 90 residues each Riittinen et al, 1996).…”

Elevated urokinase-type plasminogen activator receptor expression in a colon cancer cell line is due to a constitutively activated extracellular signal-regulated kinase-1-dependent signaling cascade

“…Several studies have shown that urokinase can bind to a 55 ± 60 kDa heavily glycosylated, disul®de linked, cell surface receptor (u-PAR) speci®cally and with high a nity (K D^0 .5 nM) (Stoppelli et al, 1986;Vassalli et al, 1985). This receptor is comprised of three similar repeats approximately 90 residues each Riittinen et al, 1996) the ®rst of which is required for the binding of urokinase and the last which is anchored to the cell membrane via a glycosyl-phosphatidylinositol chain .…”