HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 26, 25225-25232, July 1, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/26/25225    most recent M412605200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gargiulo, L. Articles by Carriero, M. V. Search for Related Content PubMed PubMed Citation Articles by Gargiulo, L. Articles by Carriero, M. V. Social Bookmarking                      What's this?

Cross-talk between fMLP and Vitronectin Receptors Triggered by Urokinase Receptor-derived SRSRY Peptide^*

Lucia Gargiulo, Immacolata Longanesi-Cattani, Katia Bifulco, Paola Franco¶, Rosanna Raiola, Pietro Campiglia||, Paolo Grieco||, Gianfranco Peluso, M. Patrizia Stoppelli¶, and Maria V. Carriero**

From the Department of Experimental Oncology, National Cancer Institute, 80131 Naples, Italy, ^¶Institute of Genetics and Biophysics, "Adriano Buzzati-Traverso," 80125 Naples, Italy, and ^||Department of Pharmaceutical Chemistry and Toxicology, University Federico II, 80131 Naples, Italy

The urokinase-type plasminogen activator receptor (uPAR) sustains cell migration through its capacity to promote pericellular proteolysis, regulate integrin function, and mediate chemotactic signaling in response to urokinase. We have characterized the early signaling events triggered by the Ser-Arg-Ser-Arg-Tyr (SRSRY) chemotactic uPAR sequence. Cell exposure to SRSRY peptide promotes directional migration on vitronectin-coated filters, regardless of uPAR expression, in a specific and dose-dependent manner, with maximal effect at a concentration level as low as 10 nM. A similar concentration profile is observed in a quantitative analysis of SRSRY-dependent cytoskeletal rearrangements, mostly consisting of filamentous structures localized in a single cell region. SRSRY analogues with alanine substitutions fail to drive F-actin formation and cell migration, indicating a critical role for each amino acid residue. As with ligand-dependent uPAR signaling, SRSRY stimulates protein kinase C activity and results in ERK1/2 phosphorylation. The involvement of the high affinity N-formyl-Met-Leu-Phe receptor (FPR) in this process is indicated by the finding that 100 nM N-formyl-Met-Leu-Phe inhibits binding of D2D3 to the cell surface, as well as SRSRY-stimulated cell migration and F-actin polarization. Moreover, cell exposure to SRSRY promotes FPR-dependent vitronectin release and increased uPAR·v5 vitronectin receptor physical association, indicating that v5 activity is regulated by the SRSRY uPAR sequence via FPR. Finally, we provide evidence that v5 is required for SRSRY-dependent ERK1/2 phosphorylation, whereas it is not required for protein kinase C activation. The data indicate that the ability of uPAR to stimulate cell migration and cytoskeletal rearrangements is retained by the SRSRY peptide alone and that it is supported by cross-talk between FPR and v5.

Received for publication, November 8, 2004 , and in revised form, April 29, 2005.

^* This work was supported by the Italian Association for Cancer Research, Ricerca Finalizzata Ministero della Salute 2003, and the European Union Framework Programme 6 (LSHC-CT-2003-503297). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^** To whom correspondence should be addressed: Dept. of Experimental Oncology, National Cancer Institute of Naples, Via M. Semmola, 80131 Naples, Italy. Tel.: 39-081-5903569; Fax: 39-081-5903814; E-mail: mariolina.carriero{at}fondazionepascale.it.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. D. Madsen, G. M. S. Ferraris, A. Andolfo, O. Cunningham, and N. Sidenius uPAR-induced cell adhesion and migration: vitronectin provides the key J. Cell Biol., June 21, 2007; 177(5): 927 - 939. [Abstract] [Full Text] [PDF]

				H. Gardsvoll and M. Ploug Mapping of the Vitronectin-binding Site on the Urokinase Receptor: INVOLVEMENT OF A COHERENT RECEPTOR INTERFACE CONSISTING OF RESIDUES FROM BOTH DOMAIN I AND THE FLANKING INTERDOMAIN LINKER REGION J. Biol. Chem., May 4, 2007; 282(18): 13561 - 13572. [Abstract] [Full Text] [PDF]

				P. Franco, I. Vocca, M. V. Carriero, D. Alfano, L. Cito, I. Longanesi-Cattani, P. Grieco, L. Ossowski, and M. P. Stoppelli Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and {alpha}v{beta}5 integrin J. Cell Sci., August 15, 2006; 119(16): 3424 - 3434. [Abstract] [Full Text] [PDF]

				D. Alfano, I. Iaccarino, and M. P. Stoppelli Urokinase Signaling through Its Receptor Protects against Anoikis by Increasing BCL-xL Expression Levels J. Biol. Chem., June 30, 2006; 281(26): 17758 - 17767. [Abstract] [Full Text] [PDF]

				R. Mazzieri, S. D'Alessio, R. K. Kenmoe, L. Ossowski, and F. Blasi An Uncleavable uPAR Mutant Allows Dissection of Signaling Pathways in uPA-dependent Cell Migration Mol. Biol. Cell, January 1, 2006; 17(1): 367 - 378. [Abstract] [Full Text] [PDF]