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

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155 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)3983-3990
期刊Journal of Biological Chemistry
出版狀態已發佈 - 2月 9 2001

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學


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