Fig.3. Beclin-1 is a physiological target of ULK kinase in response to amino acid withdrawal and mTOR inhibition.
Unless otherwise stated all experiments were repeated three times and data shown is representative. (a) Wild-type MEF were cultured with or without amino acids. ATG14L-associated Beclin-1 was immunoprecipitated and treated with lambda phosphatase treatment (PPase) as indicated. Western blot was performed with the indicated antibodies. Beclin-1 S14 phosphorylation was quantified (shown under top panel) normalized to total Beclin-1. (b) Wild-type MEF were starved for the indicated time points. Beclin-1 was immunopurified by ATG14L IP and immunoblotted as indicated (top panels). Whole cell lysates were immunoblotted with pULK1 S757 (mTORC1-target site), pS6K and ULK1 antibodies (bottom panels). Two unique experiments were performed. (c) Wild-type or FIP200 -/- MEF were incubated under nutrient rich, amino acid deprived or Torin-1 (+T, an mTOR inhibitor) conditions. Beclin-1 was purified and immunoblotted as in Fig.3b. (d) Wild-type or ULK def MEF were incubated with or without amino acids. Beclin-1 was purified and immunoblotted as in Fig.3a. Two unique experiments were performed.