An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor

Bifulco, Katia; Longanesi-Cattani, Immacolata; Gargiulo, Lucia; Maglio, Ornella; Cataldi, Mauro; De Rosa, Mario; Stoppelli, Maria Patrizia; Pavone, Vincenzo; Carriero, Maria Vincenza

doi:10.1016/j.febslet.2008.03.001

« Previous Next »FEBS Letters
Volume 582, Issue 7 , Pages 1141-1146, 2 April 2008

An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor

Edited by Veli-Pekka Lehto

Katia Bifulco
- Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy
Immacolata Longanesi-Cattani
- Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy
Lucia Gargiulo
- Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy
- Present Address: Department of Haematology, Imperial College, Faculty of Medicine, London, United Kingdom.
Ornella Maglio
- Department of Chemistry,“Federico II” University of Naples, Naples, Italy
Mauro Cataldi
- Division of Pharmacology, Department of Neuroscience, “Federico II” University of Naples, Naples, Italy
Mario De Rosa
- Department of Experimental Medicine, Second University of Naples, Naples, Italy
Maria Patrizia Stoppelli
- Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, Naples, Italy
Vincenzo Pavone
- Department of Chemistry,“Federico II” University of Naples, Naples, Italy
Maria Vincenza Carriero
- Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy
- Corresponding author. Fax: +39 0815903814.

Received 18 December 2007; received in revised form 2 March 2008; accepted 4 March 2008. published online 11 March 2008.

Abstract

Urokinase receptor (uPAR) plays a key role in physiological and pathological processes sustained by an altered cell migration. We have developed peptides carrying amino acid substitutions along the Ser⁸⁸-Arg-Ser-Arg-Tyr⁹² (SRSRY) uPAR chemotactic sequence. The peptide pyro glutamic acid (pGlu)-Arg-Glu-Arg-Tyr-NH2 (pERERY-NH₂) shares the same binding site with SRSRY and competes with N-formyl-Met-Leu-Phe (fMLF) for binding to the G-protein-coupled N-formyl-peptide receptor (FPR). pERERY-NH₂ is a dose-dependent inhibitor of both SRSRY- and fMLF-directed cell migration, and prevents agonist-induced FPR internalization and fMLF-dependent ERK1/2 phosphorylation. pERERY-NH₂ is a new and potent uPAR inhibitor which may suggest the generation of new pharmacological treatments for pathological conditions involving increased cell migration.

Abbreviations: uPAR, urokinase receptor, pGlu, pyro glutamic acid, fMLF, N-formyl-Met-Leu-Phe, FPR, N-formyl-peptide receptor