The cleavage of the urokinase receptor regulates its multiple functions

Nunzia Montuori, Maria Vincenza Carriero, Salvatore Salzano, Guido Rossi, Pia Ragno

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The urokinase-type plasminogen activator (uPA) is able to cleave its cell surface receptor (uPAR) anchored to the cell membrane through a glycophosphatidylinositol tail. The cleavage leads to the formation of cell surface truncated forms, devoid of the N-terminal domain 1 (Dl) and unmasks or disrupts, depending on the cleavage site, a sequence in the D1-D2 linker region (residues 88-92), which in the soluble form is a potent chemoattractant for monocyte-like cells. To investigate the possible role(s) of the cleaved forms of cell surface glycophosphatidylinositol-anchored uPAR, uPAR-negative human embrional kidney 293 cells were transfected with the cDNA of intact uPAR, (uPAR-293) or with cDNAs corresponding to the truncated forms of uPAR exposing (D2D3-293) or lacking (D2D3wc-293) the peptide 88-92 (P88-92). Cell adhesion assays and co-immunoprecipitation experiments indicated that the removal of D1, independently of the presence of P88-92, abolished the lateral interaction of uPAR with integrins and its capability to regulate integrin adhesive functions. The expression of intact uPAR induced also a moderate increase in 293 cell proliferation, which was accompanied by the activation of ERK. Also this effect was abolished by D1 removal, independently of the presence of P88-92. The expression of intact and truncated uPARs regulated cell directional migration toward uPA, the specific uPAR ligand, and toward fMLP, a bacterial chemotactic peptide. In fact, the uPA-dependent cell migration required the expression of intact uPAR, including D1, whereas the fMLP-dependent cell migration required the expression of a P88-92 containing uPAR and was independent of the presence of D1. Together these observations indicate that uPA-mediated uPAR cleavage and D1 removal, occurring on the cell surface of several cell types, can play a fundamental role in the regulation of multiple uPAR functions.

Original languageEnglish
Pages (from-to)46932-46939
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number49
DOIs
Publication statusPublished - Dec 6 2002

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Urokinase-Type Plasminogen Activator
Peptides
Cell Movement
Integrins
Complementary DNA
Chemotactic Factors
Cell adhesion
Cell proliferation
Cell Surface Receptors
Cell membranes
Assays
Adhesives
Immunoprecipitation
Cell Adhesion
Chemical activation
Cells
Tail
Monocytes
Ligands
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry

Cite this

The cleavage of the urokinase receptor regulates its multiple functions. / Montuori, Nunzia; Carriero, Maria Vincenza; Salzano, Salvatore; Rossi, Guido; Ragno, Pia.

In: Journal of Biological Chemistry, Vol. 277, No. 49, 06.12.2002, p. 46932-46939.

Research output: Contribution to journalArticle

Montuori, Nunzia ; Carriero, Maria Vincenza ; Salzano, Salvatore ; Rossi, Guido ; Ragno, Pia. / The cleavage of the urokinase receptor regulates its multiple functions. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 49. pp. 46932-46939.
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