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Title: | Phosphorylation of Rab5a protein by protein kinase Cϵ is crucial for T-cell migration | Authors: | Ong, Seow Theng Freeley, Michael Skubis-Zegadło, Joanna Fazil, Mobashar Hussain Urf Turabe Kelleher, Dermot Fresser, Friedrich Baier, Gottfried Verma, Navin Kumar Long, Aideen |
Keywords: | DRNTU::Science::Biological sciences | Issue Date: | 2014 | Source: | Ong, S. T., Freeley, M., Skubis-Zegadło, J., Fazil, M. H. U. T., Kelleher, D., Fresser, F., et al. (2014). Phosphorylation of Rab5a protein by protein kinase Cϵ is crucial for T-cell migration. Journal of biological chemistry, 289(28), 19420-19434. | Series/Report no.: | Journal of biological chemistry | Abstract: | Rab GTPases control membrane traffic and receptor-mediated endocytosis. Within this context, Rab5a plays an important role in the spatial regulation of intracellular transport and signal transduction processes. Here, we report a previously uncharacterized role for Rab5a in the regulation of T-cell motility. We show that Rab5a physically associates with protein kinase C ε (PKC ε ) in migrating T-cells. Following stimulation of T- cells through the integrin LFA-1 or the chemokine receptor CXCR4, Rab5a is phosphorylated on a N-terminal T7 site by PKC ε . Both Rab5a and PKC ε dynamically interact at the centrosomal region of migrating cells, and PKC ε -mediated phosphorylation on T7 regulates Rab5a trafficking to the cell leading edge. Further, we demonstrate that Rab5a T7 phosphorylation is functionally necessary for Rac1 activation, actin rearrangement and T- cell motility. We present a novel mechanism by which a PKC ε -Rab5a-Rac1 axis regulates cytoskeleton remodelling and T-cell migration, both of which are central for the adaptive immune response. | URI: | https://hdl.handle.net/10356/105810 http://hdl.handle.net/10220/20966 |
DOI: | 10.1074/jbc.M113.545863 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Rights: | © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Biological Chemistry, The American Society for Biochemistry and Molecular Biology, Inc. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1074/jbc.M113.545863]. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
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Phosphorylation of Rab5a by Protein Kinase Cε is Crucial for T-cell Migration.pdf | Main article | 2.37 MB | Adobe PDF | View/Open |
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