Urokinase-type Plasminogen Activator Receptor (CD87) Is a Ligand for Integrins and Mediates Cell-Cell Interaction

Takehiko Tarui, Andrew P. Mazar, Douglas B. Cines, Yoshikazu Takada

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Binding of urokinase-type plasminogen activator (uPA) to its receptor (UPAR/CD87) regulates cellular adhesion, migration, and tumor cell invasion. However, it is unclear how glycosyl phosphatidylinositol-anchored UPAR, which lacks a transmembrane structure, mediates signal transduction. It has been proposed that UPAR forms cis-interactions with integrins as an associated protein and thereby transduces proliferative or migratory signals to cells upon binding of uPA. We provide evidence that soluble UPAR (suPAR) specifically binds to integrins α4β1, α6β1, α9β1, and αvβ3 on Chinese hamster ovary cells in a cation-dependent manner. Anti-integrin and anti-uPAR antibodies effectively block binding of suPAR to these integrins. Binding of suPAR to α4β1 and αvβ3 is blocked by known soluble ligands and by the integrin mutations that inhibit ligand binding. These results suggest that UPAR is an integrin ligand rather than, or in addition to, an integrin-associated protein. In addition, we demonstrate that glycosyl phosphatidylinositol-anchored uPAR on the cell surface specifically binds to integrins on the apposing cells, suggesting that uPAR-integrin interaction may mediate cell-cell interaction (trans-interaction). These previously unrecognized uPAR-integrin interactions may allow uPAR to transduce signals through the engaged integrin without a hypothetical transmembrane adapter and may provide a potential therapeutic target for control of inflammation and cancer.

Original languageEnglish
Pages (from-to)3983-3990
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number6
DOIs
Publication statusPublished - Feb 9 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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