Phosphorylation of Rab5a protein by protein kinase Cϵ Is crucial for T-cell migration
File Type:
PDFItem Type:
Journal ArticleDate:
2014Author:
Access:
openAccessCitation:
Ong, S.T., Freeley, M., Skubis-Zegad, J., Hussain Urg Turabe Fazil, M., Kelleher, D., Fresser, F., Baier, G., Verma, N.K. & Long, A., Phosphorylation of Rab5a protein by protein kinase Cϵ Is crucial for T-cell migration, Journal of Biological Chemistry, 289, 28, 2014, 19420-19434Download Item:
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.
Author's Homepage:
http://people.tcd.ie/longaiDescription:
PUBLISHED
Author: Long, Aideen; Ong, Seow Theng; Freeley, Michael; Skubis-Zegladło, Joanna; Hussain Urf Turabe Fazil, Mobashar; Kelleher, Dermot; Fresser, Friedrich; Baier, Gottfried; Verma, Navin K.
Type of material:
Journal ArticleCollections
Series/Report no:
Journal of Biological Chemistry;289;
28;
Availability:
Full text availableKeywords:
Rab GTPases control membrane traffic and receptor-mediated endocytosis, Cell migration, Cell signaling, Immunology, Integrin, Phosphorylation, Rab proteins, Signal transduction, T-cellDOI:
http://dx.doi.org/10.1074/jbc.M113.545863Metadata
Show full item recordLicences: