[HTML][HTML] S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-α signaling through IKK2

J Zhang, Z Gao, J Yin, MJ Quon, J Ye - Journal of Biological Chemistry, 2008 - ASBMB
S6K1 (p70S6K) is a serine kinase downstream from Akt in the insulin signaling pathway that
is involved in negative feedback regulation of insulin action. S6K1 is also activated by TNF-
α, a pro-inflammatory cytokine. However, its role remains to be characterized. In the current
study, we elucidated a mechanism for S6K1 to mediate TNF-α-induced insulin resistance in
adipocytes and hepatocytes. S6K1 was phosphorylated at Thr-389 in response to TNF-α.
This led to phosphorylation of IRS-1 by S6K1 at multiple serine residues including Ser-270 …