title: TRAF6 is required for the GM-CSF-induced JNK, p38 and Akt activation.
abstract: JNK, p38 and Akt signalings have been shown to be activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and are pivotal for GM-CSF-mediated survival, proliferation and differentiation of macrophages and their progenitors. However, the detailed mechanism of how these signalings is activated by GM-CSF is not fully elucidated. We report here that E3 ligase TRAF6 is required for the GM-CSF-induced activation of JNK, p38 and Akt. GM-CSF triggers autoubiquitination of TRAF6 and TRAF6 knocked down results in impaired activation of JNK and p38 signaling. TRAF6 is also required for GM-CSF-induced ubiquitination and activation of Akt. These findings reveal novel roles of TRAF6 in GM-CSF signaling.
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China; Department of Infectious Diseases, Chinese PLA 532 Hospital, Anhui 242700, China.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Huo
authors.affiliation: 307-lvy Translational Medicine Center, Laboratory of Oncology, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jing
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China. Electronic address: yxgck307@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China; 307-lvy Translational Medicine Center, Laboratory of Oncology, Chinese PLA 307 Hospital, Beijing 100071, China. Electronic address: marbleluo@126.com.
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D055785:Gene Knockdown Techniques; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000276:immunology*; D054875:Ubiquitination / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D048029:TNF Receptor-Associated Factor 6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Akt; GM-CSF; JNK; TRAF6; p38