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

• GM-CSF promotes K63-linked polyubiquitin chain modification of TRAF6.
• TRAF6 is required for the GM-CSF-induced activation of JNK and p38.
• TRAF6 is required for the GM-CSF-induced Akt ubiquitination and activation.
• Depletion of TRAF6 results in defective in GM-CSF-induced cell growth.

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.