Filamin A phosphorylation by Akt promotes cell migration in response to arsenic

摘要: // Lingzhi Li 1 , Yongju Lu Paul M. Stemmer 1, 2 Fei Chen Department of Pharmaceutical Sciences, Eugene Applebaum College Pharmacy and Health Wayne State University, Detroit, MI 48201, USA The Proteomics Core Institute Environmental School Medicine, Correspondence to: Chen, e-mail: fchen@wayne.edu Keywords: arsenic, Akt, filamin A, migration, patient survival Received: February 12, 2015      Accepted: March 14, Published: April 03, 2015 ABSTRACT We had previously reported that trivalent arsenic (As 3+ ), a well-known environmental carcinogen, induces phosphorylation several putative Akt substrates. In the present report, we characterized one these substrates by immunoprecipitation proteomics analysis. results indicate cytoskeleton remodeling protein, with molecular weight around 280 kDa, is phosphorylated in HEK-293 cells treated As which was also confirmed human bronchial epithelial cell line, BEAS-2B cells. Additional biochemical biological studies revealed serine 2152 (S2152) A activated . To further confirm importance Akt-dependent S2152 -induced over-expressed either wild type or mutated substituted alanine (S2152A). capability migration reduced significantly expressing Clinically, found increased expression predicts poorer overall lung cancer patients adenocarcinoma. Thus, data suggest dependent key events mediating carcinogenesis. Antagonizing signaling can ameliorate may serve as targeting strategy for malignancies associated exposure.