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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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Volume 383, Issue 1


Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions

Maria Vincenza Carriero / Paola Franco / Lucia Gargiulo / Immacolata Vocca / Letizia Cito / Laura Fontana / Ciro Iaccarino / Giovanna Del Pozzo / John Guardiola / Maria Patrizia Stoppelli
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2002.011


We have previously reported that phosphorylation of human urokinase on Ser138/303 abolishes its catalyticindependent motogen and proadhesive abilities, whereas receptor binding is not affected. Here we show that substitution of the two relevant serines with glutamic acid residues impairs the ability of urokinase to mobilize a variety of human and mouse cell lines as well as human primary T lymphocytes. Accordingly, urokinase receptordependent signaling, leading to cytoskeletal rearrangements and paxillin redistribution, does not occur in MCF-7 breast carcinoma cells exposed to phosphorylationlike urokinase. Unlike the wildtype form, disubstituted urokinase is unable to induce the physical association of urokinase receptor with αvβ5 vitronectin receptor, which is required for MCF-7 urokinasedependent cell migration. Finally, the disubstituted variant fails to activate p55fgr, a member of the Src tyrosine kinase family, which mediates cell migration and adhesion of U937 myelomonocytic cells. In conclusion, the finding that specific amino acid substitutions strongly interfere with the ability of urokinase to stimulate cell migration, and the associated intracellular events uncover a novel way to regulate urokinase receptordependent signaling.

About the article

Published Online: 2005-06-01

Published in Print: 2002-01-23

Citation Information: Biological Chemistry, Volume 383, Issue 1, Pages 107–113, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2002.011.

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