“…Akt and Erk1/2 phosphorylate TSC2 to inhibit the TSC complex by disrupting the association between TSC1 and TSC2 (Ma, Chen, Erdjument‐Bromage, Tempst, & Pandolfi, 2005; Menon et al, 2014). In contrast, under stress conditions such as energy depletion resulting in an increased AMP to ATP ratio, the protein kinase AMPK is activated through phosphorylation by upstream kinases, such as LKB1 (Hardie, Ross, & Hawley, 2012), and phosphorylates TSC2 to enhance its GAP activity (Inoki, Zhu, & Guan, 2003). Thus, since the TSC complex integrates multiple upstream signals to negatively regulate a key step in mTORC1 activation, its disruption causes constitutive mTORC1 activation (Byles et al, 2013; Castets et al, 2013; Kwiatkowski et al, 2002).…”