%0 Journal Article
%T 14-3-3¦Æ Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells
%A Jia Zhang
%A Fangjin Chen
%A Wenliang Li
%A Qian Xiong
%A Mingkun Yang
%A Peng Zheng
%A Chongyang Li
%A Jianfeng Pei
%A Feng Ge
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0029554
%X The 14-3-3 proteins are a family of regulatory signaling molecules that interact with other proteins in a phosphorylation-dependent manner and function as adapter or scaffold proteins in signal transduction pathways. One family member, 14-3-3¦Æ, is believed to function in cell signaling, cycle control, and apoptotic death. A systematic proteomic analysis done in our laboratory has identified signal transducers and activators of transcription 3 (Stat3) as a novel 14-3-3¦Æ interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3¦Æ interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3¦Æ interaction and mutation of Ser727 to Alanine abolished 14-3-3¦Æ/Stat3 association. Inhibition of 14-3-3¦Æ protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3¦Æ is involved in the regulation of protein kinase C (PKC) activity and 14-3-3¦Æ binding to Stat3 protects Ser727 dephosphorylation from protein phosphatase 2A (PP2A). Taken together, our findings support the model that multiple signaling events impinge on Stat3 and that 14-3-3¦Æ serves as an essential coordinator for different pathways to regulate Stat3 activation and function in MM cells.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029554