An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor.
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.
Bifulco
Katia
K
Department of Experimental Oncology, National Cancer Institute of Naples, via M. Semmola, 80131 Naples, Italy.
Longanesi-Cattani
Immacolata
I
Gargiulo
Lucia
L
Maglio
Ornella
O
Cataldi
Mauro
M
De Rosa
Mario
M
Stoppelli
Maria Patrizia
MP
Pavone
Vincenzo
V
Carriero
Maria Vincenza
MV
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
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