TRAF6 is required for the GM-CSF-induced JNK, p38 and Akt activation

Yiwu Wang; Chenchen Zhou; Jiang Huo; Yanli Ni; Pengfei Zhang; Cheng Lu; Bin Jing; Fengjun Xiao; Wenxia Chen; Wei Li; Peng Zhang; Luo Zhang

doi:10.1016/j.molimm.2015.01.012

TRAF6 is required for the GM-CSF-induced JNK, p38 and Akt activation

Mol Immunol. 2015 Jun;65(2):224-9. doi: 10.1016/j.molimm.2015.01.012. Epub 2015 Feb 17.

Authors

Yiwu Wang¹, Chenchen Zhou², Jiang Huo³, Yanli Ni⁴, Pengfei Zhang², Cheng Lu², Bin Jing², Fengjun Xiao⁵, Wenxia Chen², Wei Li², Peng Zhang⁶, Luo Zhang⁷

Affiliations

¹ Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China; Department of Infectious Diseases, Chinese PLA 532 Hospital, Anhui 242700, China.
² Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China.
³ Department of Anesthesiology, Chinese PLA 307 Hospital, Beijing 100071, China.
⁴ 307-lvy Translational Medicine Center, Laboratory of Oncology, Chinese PLA 307 Hospital, Beijing 100071, China.
⁵ Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
⁶ Department of Biomedical Engineering, Chinese PLA 307 Hospital, Beijing 100071, China. Electronic address: [email protected].
⁷ 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: [email protected].

PMID: 25700345
DOI: 10.1016/j.molimm.2015.01.012

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.

Keywords: Akt; GM-CSF; JNK; TRAF6; p38.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Enzyme Activation / genetics
Enzyme Activation / immunology
Gene Knockdown Techniques
Granulocyte-Macrophage Colony-Stimulating Factor / genetics
Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
MAP Kinase Kinase 4 / genetics
MAP Kinase Kinase 4 / immunology*
MAP Kinase Signaling System / genetics
MAP Kinase Signaling System / immunology*
Macrophages / cytology
Macrophages / immunology*
Mice
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / immunology*
TNF Receptor-Associated Factor 6 / genetics
TNF Receptor-Associated Factor 6 / immunology*
Ubiquitination / genetics
Ubiquitination / immunology
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / immunology*

Substances

TNF Receptor-Associated Factor 6
Granulocyte-Macrophage Colony-Stimulating Factor
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4