PKCε controls the traffic of β1 integrins in motile cells
PKCε controls the traffic of β1 integrins in motile cells
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DOI：
10.1093/emboj/cdf371
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发表时间：
2002-07-15
期刊：
影响因子：
11.4
通讯作者：
Parker, PJ
中科院分区：
文献类型：
--
作者：
Ivaska, J;Whelan, RDH;Parker, PJ
蛋白激酶C （PKC）参与了β a1整合素介导的细胞迁移。新的PKC异构体PKCepsilon在PKCepsilon（-/-）细胞中的表达，以依赖于PKC催化活性的方式刺激细胞向β 1整合素底物的定向迁移。在PKC抑制作用下，整合素β 1和PKCepsilon可逆地被困在CD81阳性的细胞内腔室中，与趋近性降低相关。免疫荧光和脉冲标记研究表明，这是一个以前未被表征的被PKC抑制的循环室。电镜显示PKCepsilon和整合素β 1在囊泡膜上共定位。最后，利用体外重构系统，PKCepsilon与这些囊泡的解离被证明依赖于细胞质成分和能量的存在，以及PKC的催化活性。目前的证据表明，PKCepsilon控制一个内部运输步骤，在不受抑制的条件下允许β 1整合素的再循环，促进细胞运动。
Protein kinase C (PKC) has been implicated in beta1 integrin-mediated cell migration. Expression of the novel PKC isoform, PKCepsilon, in PKCepsilon(-/-) cells is shown here to stimulate directional migration of cells towards beta1 integrin substrates in a manner dependent on PKC catalytic activity. On PKC inhibition, integrin beta1 and PKCepsilon become reversibly trapped in a tetraspanin (CD81)-positive intracellular compartment, correlating with reduced haptotaxis. Immunofluorescence and pulse labelling studies indicate that this is a previously uncharacterized recycling compartment trapped by inhibition of PKC. Electron microscopy demonstrated the co-localization of PKCepsilon and integrin beta1 on the vesicular membranes. Finally, using a reconstituted in vitro system, the dissociation of PKCepsilon from these vesicles is shown to be dependent on both the presence of cytosolic components and energy, and on PKC catalytic activity. The evidence presented indicates that PKCepsilon controls an internal traffic step that under uninhibited conditions permits the recycling of beta1 integrin, contributing to cell motility.