期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 28, 页码 19420-19434出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.545863
关键词
-
资金
- Science Foundation Ireland
- Higher Education Authority of Ireland under PRTLI cycle 3
- Health Research Board of Ireland
- Marie Curie [MTKDCT-2005-029798]
- NTU-MOE start-up grant
- FWF Austrian Science Fund [P19505-B05]
- European Community Program SYBILLA [HEALTH-F4-2008-201106]
- Austrian Science Fund (FWF) [P 25044] Funding Source: researchfish
- Austrian Science Fund (FWF) [P19505] Funding Source: Austrian Science Fund (FWF)
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 epsilon (PKC epsilon) 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 epsilon. Both Rab5a and PKC epsilon dynamically interact at the centrosomal region of migrating cells, and PKC epsilon-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 epsilon-Rab5a-Rac1 axis regulates cytoskeleton remodeling and T-cell migration, both of which are central for the adaptive immune response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据