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[摘要]：Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a transforming gene product that is highly expressed in human tumors of the ovary, lung, and breast. eEF1A2 also stimulates actin remodeling, and the expression of this factor is sufficient to induce the formation of filopodia, long cellular processes composed of bundles of parallel actin filaments. Here, we find that eEF1A2 stimulates formation of filopodia by increasing the cellular abundance of cytosolic and plasma membrane-bound phosphatidylinositol-4,5 bisphosphate [PI(4,5)P-2]. We have previously reported that the eEF1A2 protein binds and activates phosphatidylinositol-4 kinase III beta (PI4KIII beta), and we find that production of eEF1A2-dependent PI(4,5)P-2 and generation of filopodia require PI4KIII beta. Furthermore, PI4KIII beta is itself capable of activating both the production of PI(4,5)P-2 and the creation of filopodia. We propose a model for extrusion of filopodia in which eEF1A2 activates P14KIII beta, and activated PI4KIII beta stimulates production of PI(4,5)P-2 and filopodia by increasing PI4P abundance. Our work suggests an important role for both eEF1A2 and P14KIII beta in the control of PI(4,5)P-2 signaling and actin remodeling. |
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