EGF increases mTORC1 signaling in a TBK1‐dependent manner. TBK1+/+ and TBK1−/− MEFs were serum‐starved (20 h), pre‐treated with Ku‐0063794 [1 μM] (30 min), and stimulated −/+ EGF [25 ng/ml] (0–60 min). Whole‐cell lysates (WCL) were immunoblotted (IB) as indicated.
Ectopic expression of TBK1 rescues mTORC1 signaling in TBK1−/− MEFs. TBK1−/− MEFs were transiently transfected with vector control (V), wild type (WT), or kinase‐dead (KD) Flag‐TBK1, serum‐starved (20 h), and analyzed as above.
EGF‐receptor signaling remains intact in TBK1−/− MEFs. TBK1+/+ and TBK1−/− MEFs were serum‐starved (20 h) and stimulated −/+ EGF [25 ng/ml] (0, 5, or 15 min).
TBK1 is required for EGF‐stimulated mTORC1 and mTORC2 signaling. TBK1+/+ and TBK1−/− MEFs were stimulated with EGF as in (A).
TBK1 is not required for insulin‐stimulated mTORC1 signaling. TBK1+/+ and TBK1−/− MEFs were stimulated with insulin as in (C).
Side‐by‐side comparison of EGF‐ vs. insulin‐stimulated mTORC1 and mTORC2 signaling in TBK1+/+ vs. TBK1−/− MEFs. MEFs were treated as in (C).
Pharmacologic TBK1 inhibition reduces EGF‐induced mTORC1 signaling. HEK293 cells were serum‐starved (20 h), pre‐treated with Ku‐0063794 [1 μM] (30 min) or amlexanox [50 μM] (2 h), and stimulated −/+ EGF [25 ng/ml] (30 min) or insulin (INS) [100 nM] (30 min).
EGF but not insulin increases mTOR P‐S2159. TBK1+/+ vs. TBK1−/− MEFs: MEFs were treated as in (C). The arrow indicates mTOR phosphorylated on S2159.