cortactin phosphorylated by erk12 localizes to sites of dynamic actin regulation and is required for carcinoma lamellipodia persistencecortactin磷酸化erk12定位网站的动态肌动蛋白需要监管和癌板状伪足持久性.pdfVIP

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cortactin phosphorylated by erk12 localizes to sites of dynamic actin regulation and is required for carcinoma lamellipodia persistencecortactin磷酸化erk12定位网站的动态肌动蛋白需要监管和癌板状伪足持久性.pdf

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cortactin phosphorylated by erk12 localizes to sites of dynamic actin regulation and is required for carcinoma lamellipodia persistencecortactin磷酸化erk12定位网站的动态肌动蛋白需要监管和癌板状伪足持久性

Cortactin Phosphorylated by ERK1/2 Localizes to Sites of Dynamic Actin Regulation and Is Required for Carcinoma Lamellipodia Persistence . . . Laura C. Kelley , Karen E. Hayes , Amanda Gatesman Ammer , Karen H. Martin, Scott A. Weed* Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, United States of America Abstract Background: Tumor cell motility and invasion is governed by dynamic regulation of the cortical actin cytoskeleton. The actin-binding protein cortactin is commonly upregulated in multiple cancer types and is associated with increased cell migration. Cortactin regulates actin nucleation through the actin related protein (Arp)2/3 complex and stabilizes the cortical actin cytoskeleton. Cortactin is regulated by multiple phosphorylation events, including phosphorylation of S405 and S418 by extracellular regulated kinases (ERK)1/2. ERK1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the Arp2/3 regulator neuronal Wiskott-Aldrich syndrome protein (N-WASp), promoting actin polymerization and enhancing tumor cell movement. Methodology/Principal Findings: In this report we have developed phosphorylation-specific antibodies against phosphorylated cortactin S405 and S418 to analyze the subcellular localization of this cortactin form in tumor cells and patient samples by microscopy. We evaluated the interplay between cortactin S405 and S418 phosphorylation with cortactin tyrosine phosphorylation in regulating cortactin confo