title: An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor.
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.
authors.affiliation: Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Bifulco
authors.forename: Immacolata
authors.initials: I
authors.lastname: Longanesi-Cattani
authors.forename: Lucia
authors.initials: L
authors.lastname: Gargiulo
authors.forename: Ornella
authors.initials: O
authors.lastname: Maglio
authors.forename: Mauro
authors.initials: M
authors.lastname: Cataldi
authors.forename: Mario
authors.initials: M
authors.lastname: De Rosa
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Stoppelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Carriero
mesh_terms: D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009842:Oligopeptides; C524898:PLAUR protein, human; D010455:Peptides; C524900:Plaur protein, rat; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D055293:Receptors, Urokinase Plasminogen Activator; C529347:pyroglutamyl-arginyl-glutamyl-arginyl-tyrosinamide