ENDOCYTOSIS OF UROKINASE-PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 COMPLEXES BOUND TO A CHIMERIC TRANSMEMBRANE UROKINASE RECEPTOR

Citation
H. Li et al., ENDOCYTOSIS OF UROKINASE-PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 COMPLEXES BOUND TO A CHIMERIC TRANSMEMBRANE UROKINASE RECEPTOR, The Journal of biological chemistry, 269(11), 1994, pp. 8153-8158
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
269
Issue
11
Year of publication
1994
Pages
8153 - 8158
Database
ISI
SICI code
0021-9258(1994)269:11<8153:EOUAIT>2.0.ZU;2-E
Abstract
The urokinase receptor (uPAR) is linked to plasma membranes through a glycosylphosphatidylinositol (GPI) anchor. It has been posited that th e GPI anchor facilitates clearance of uPAR-bound complexes between two chain urokinase (tcuPA) and plasminogen activator inhibitor type 1 (P AI-1) by the alpha(2)-macroglobulin receptor (alpha(2)MR) which permit s re-expression of unoccupied uPA receptors on the cell surface. To te st this hypothesis we compared internalization and degradation of I-12 5-labeled tcuPA.PAI-1 by COS cells expressing either transfected wild- type, GPI-linked uPAR (uPAR/GPI), or a chimeric receptor composed of t he extracellular domains of uPAR linked to the transmembrane and cytos olic domains of the alpha chain (p55 subunit) of the interleukin-2 rec eptor (uPAR/IL-2R(alpha)). The kinetics of binding, internalization an d degradation of tcuPA.PAI-1 by COS cells expressing each form of uPAR were virtually identical. However, internalization of complexes by uP AR/IL-2R(alpha) was more susceptible to inhibition by recombinant solu ble 39-kDa alpha(2)MR-associated protein (RAP) which competes for bind ing of tcuPA.PAI-1 complexes to alpha(2)MR (p < 0.001), and the intern alization was accompanied by a greater reduction in the number of surf ace uPAR/IL-2R(alpha), than uPAR/GPI (p < 0.05). These studies indicat e that the rate of internalization of tcuPA. PAI-1 is governed primari ly by the extracellular domains of uPAR, whereas the GPI anchor may fa cilitate internalization of complexes and re-expression of uPAR when b inding sites on (alpha(2)MR are limiting.