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

被引：47

作者：

Bifulco, Katia ^{[1
]}

Longanesi-Cattani, Immacolata ^{[1
]}

Gargiulo, Lucia ^{[1
]}

Maglio, Ornella ^{[2
]}

Cataldi, Mauro ^{[3
]}

De Rosa, Mario ^{[4
]}

Stoppelli, Maria Patrizia ^{[5
]}

Pavone, Vincenzo ^{[2
]}

Carriero, Maria Vincenza ^{[1
]}

机构：

[1] Natl Canc Inst Naples, Dept Expt Oncol, I-80131 Naples, Italy

[2] Univ Naples Federico 2, Dept Chem, Naples, Italy

[3] Univ Naples Federico 2, Dept Neurosci, Div Pharmacol, Naples, Italy

[4] Univ Naples 2, Dept Expt Med, Naples, Italy

[5] Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy

来源：

FEBS LETTERS | 2008年 / 582卷 / 07期

关键词：

inhibitors of cell migration; formyl-peptide receptor; urokinase receptor;

D O I：

10.1016/j.febslet.2008.03.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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-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 pbosphorylation. 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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1141 / 1146

页数：6

共 26 条

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