dc.contributor.author | FREELEY, MICHAEL | en |
dc.date.accessioned | 2016-01-07T15:46:54Z | |
dc.date.available | 2016-01-07T15:46:54Z | |
dc.date.issued | 2014 | en |
dc.date.submitted | 2014 | en |
dc.identifier.citation | Ong ST, Freeley M, Skubis-Zegadło J, Fazil MH, Kelleher D, Fresser F, Baier G, Verma NK, Long A, Phosphorylation of Rab5a Protein by Protein Kinase Cϵ Is Crucial for T-cell Migration., Journal of Biological Chemistry, 298, 28, 2014, 19420 - 19434 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/75521 | |
dc.description | PUBLISHED | en |
dc.description.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 Cϵ (PKCϵ) in migrating T-cells. After stimulation of T-cells through the integrin LFA-1 or the chemokine receptor CXCR4, Rab5a is phosphorylated on an N-terminal Thr-7 site by PKCϵ. Both Rab5a and PKCϵ dynamically interact at the centrosomal region of migrating cells, and PKCϵ-mediated phosphorylation on Thr-7 regulates Rab5a trafficking to the cell leading edge. Furthermore, we demonstrate that Rab5a Thr-7 phosphorylation is functionally necessary for Rac1 activation, actin rearrangement, and T-cell motility. We present a novel mechanism by which a PKCϵ-Rab5a-Rac1 axis regulates cytoskeleton remodeling and T-cell migration, both of which are central for the adaptive immune response. | en |
dc.format.extent | 19420 | en |
dc.format.extent | 19434 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Journal of Biological Chemistry | en |
dc.relation.ispartofseries | 298 | en |
dc.relation.ispartofseries | 28 | en |
dc.rights | Y | en |
dc.subject | Cell migration | en |
dc.title | Phosphorylation of Rab5a Protein by Protein Kinase Cϵ Is Crucial for T-cell Migration. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/freeleym | en |
dc.identifier.rssinternalid | 95500 | en |
dc.rights.ecaccessrights | openAccess | |
dc.identifier.orcid_id | 0000-0002-5763-6582 | en |