An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor |
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Authors: | Bifulco Katia Longanesi-Cattani Immacolata Gargiulo Lucia Maglio Ornella Cataldi Mauro De Rosa Mario Stoppelli Maria Patrizia Pavone Vincenzo Carriero Maria Vincenza |
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Institution: | Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy. |
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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 Ser(88)-Arg-Ser-Arg-Tyr(92) (SRSRY) uPAR chemotactic sequence. The peptide pyro glutamic acid (pGlu)-Arg-Glu-Arg-Tyr-NH2 (pERERY-NH(2)) 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-NH(2) 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-NH(2) is a new and potent uPAR inhibitor which may suggest the generation of new pharmacological treatments for pathological conditions involving increased cell migration. |
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Keywords: | uPAR urokinase receptor pGlu pyro glutamic acid fMLF N-formyl-Met-Leu-Phe FPR N-formyl-peptide receptor |
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