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Phosphorylation of Rab5a protein by protein kinase C? is crucial for T-cell migration.


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? (PKC?) 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 PKC?. Both Rab5a and PKC? dynamically interact at the centrosomal region of migrating cells, and PKC?-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 PKC?-Rab5a-Rac1 axis regulates cytoskeleton remodeling and T-cell migration, both of which are central for the adaptive immune response.

SUBMITTER: Ong ST 

PROVIDER: S-EPMC4094053 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Phosphorylation of Rab5a protein by protein kinase Cϵ is crucial for T-cell migration.

Ong Seow Theng ST   Freeley Michael M   Skubis-Zegadło Joanna J   Fazil Mobashar Hussain Urf Turabe MH   Kelleher Dermot D   Fresser Friedrich F   Baier Gottfried G   Verma Navin Kumar NK   Long Aideen A  

The Journal of biological chemistry 20140528 28


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  ...[more]

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