Phosphorylation of Rab5a Protein by Protein Kinase Cϵ Is Crucial for T-cell Migration.
Item Type:Journal Article
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
J. Biol. Chem.-2014-Ong-19420-34.pdf (PDF) 3.682Mb
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: FREELEY, MICHAEL
Type of material:Journal Article
Series/Report no:Journal of Biological Chemistry
Availability:Full text available