Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and αvβ5 integrin

Paola Franco, Immacolata Vocca, Maria V. Carriero, Daniela Alfano, Letizia Cito, Immacolata Longanesi-Cattani, Paola Grieco, Liliana Ossowski, Maria P. Stoppelli

Research output: Contribution to journalArticle

Abstract

The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined 'connecting peptide' (residues 132-158) and cell-surface integrin αvβ5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to αvβ5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-αvβ5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which - through individual domains - can engage two different surface receptors (uPAR and αvβ5 integrin), thus initiating and potentiating intracellular signaling and migration.

Original languageEnglish
Pages (from-to)3424-3434
Number of pages11
JournalJournal of Cell Science
Volume119
Issue number16
DOIs
Publication statusPublished - Aug 15 2006

Keywords

  • Cytoskeleton
  • uPA
  • uPAR signaling

ASJC Scopus subject areas

  • Cell Biology

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    Franco, P., Vocca, I., Carriero, M. V., Alfano, D., Cito, L., Longanesi-Cattani, I., Grieco, P., Ossowski, L., & Stoppelli, M. P. (2006). Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and αvβ5 integrin. Journal of Cell Science, 119(16), 3424-3434. https://doi.org/10.1242/jcs.03067