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      Proteomic analysis of tyrosine phosphorylation during human liver transplantation

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          Abstract

          Background

          Ischemia-reperfusion (I/R) causes a dramatic reprogramming of cell metabolism during liver transplantation and can be linked to an alteration of the phosphorylation level of several cellular proteins. Over the past two decades, it became clear that tyrosine phosphorylation plays a pivotal role in a variety of important signalling pathways and was linked to a wide spectrum of diseases. Functional profiling of the tyrosine phosphoproteome during liver transplantation is therefore of great biological significance and is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel therapeutic strategies.

          Results

          Using liver biopsies collected during the early phases of organ procurement and transplantation, we aimed at characterizing the global patterns of tyrosine phosphorylation during hepatic I/R. A proteomic approach, based on the purification of tyrosine phosphorylated proteins followed by their identification using mass spectrometry, allowed us to identify Nck-1, a SH 2/SH 3 adaptor, as a potential regulator of I/R injury. Using immunoblot, cell fractionation and immunohistochemistry, we demonstrate that Nck-1 phosphorylation, expression and localization were affected in liver tissue upon I/R. In addition, mass spectrometry identification of Nck-1 binding partners during the course of the transplantation also suggested a dynamic interaction between Nck-1 and actin during I/R.

          Conclusion

          Taken together, our data suggest that Nck-1 may play a role in I/R-induced actin reorganization, which was previously reported to be detrimental for the hepatocytes of the transplanted graft. Nck-1 could therefore represent a target of choice for the design of new organ preservation strategies, which could consequently help to reduce post-reperfusion liver damages and improve transplantation outcomes.

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          Most cited references32

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          Signal transduction by receptors with tyrosine kinase activity.

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            Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling.

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              Protein modules and signalling networks.

              T. Pawson (1995)
              Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.
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                Author and article information

                Journal
                Proteome Sci
                Proteome Science
                BioMed Central (London )
                1477-5956
                2007
                2 January 2007
                : 5
                : 1
                Affiliations
                [1 ]Department of Surgery, McGill University, Montreal, Quebec, Canada
                [2 ]Genome Québec Innovation Centre, McGill University, Montreal, Quebec, Canada
                [3 ]Departement of Medecine, McGill University, Montreal, Quebec, Canada
                [4 ]Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada
                [5 ]Team AVENIR, INSERM E362, Université Bordeaux 2, Bordeaux, France
                [6 ]CEA/Grenoble, Grenoble, France
                Article
                1477-5956-5-1
                10.1186/1477-5956-5-1
                1769479
                17199894
                34640e2f-baba-41c5-bc63-48985147adaf
                Copyright © 2007 Emadali et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 September 2006
                : 2 January 2007
                Categories
                Research

                Molecular biology
                Molecular biology

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