The Urokinase Receptor and Cell Migration

Abstract

The receptor (u-PAR) for urokinase plasminogen activator (u-PA) is a three-domain protein, GPI-anchored to the cell surface, which focuses the enzymatic activity of u-PA, and allows the cell surface activation of plasminogen. Regulation of the activity of u-PA is also mediated by u-PAR. In fact, while active u-PA is not internalized or degraded, rather remaining active at the cell surface, serpininactivated u-PA is internalized, through the intervention of a second molecule, the α₂-macroglobulin receptor (LRP). In the process u-PAR too is internalized and possibly recycles back to the cell surface. In addition, u-PAR occupancy can also directly transduce migratory signals, like chemotaxis, that do not require the protease activity of u-PA. Occupancy of u-PAR activates tyrosine kinases, in particular of p56/p59hck, through an as yet undefined transmembrane adaptor.

Keywords:

Urokinase plasminogen activator (u-PA) - plasminogen - u-PA receptor (u-PAR) - α₂-macroglobulin receptor (LRP) - tyrosine kinase