The Inoki lab focuses on investigating the molecular mechanisms of cellular energy sensing and the roles of protein kinases such as mechanistic target of rapamycin (mTOR) and AMP-activated kinase in the regulation of cell growth, proliferation and survival control. Dys-regulation of mTOR and AMPK signaling has been implicated in a wide array of human health problems including cancer, diabetes, neurodegenerative diseases, and aging. Our group takes biochemical approaches to identify novel interacting proteins and signal transduction to expand our understandings of cellular energy sensing mechanism. Then, we take genetic approaches to clarify our biochemical observations and to seek pathophysiological relevance in mouse models. Our main goal is to elucidate the molecular mechanisms underlying dys-regulation of mTOR and AMPK pathway-associated metabolic disorders and cancer development.
- Suzuki T, Bridges D, Nakada D, Skiniotis G, Morrison SJ, Lin J, Saltiel AR, Inoki K. (2013) Inhibition of AMPK catabolic action by GSK3. Mol Cell, In press
- Inoki K, Kim J, Guan KL. (2012) AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol 10, 381-400.
- Yoshida S, Hong S, Suzuki T, Nada S, Mannan AM, Wang J, Okada M, Guan KL, Inoki K. (2011) Redox regulates mTORC1 activity by modulating the TSC1/TSC2-Rheb pathway. J BiolChem 286, 326251-60.
- Inoki K*, Mori H, Wang J, Suzuki T, Hong S, Yoshida S, Blattner SM, Ikenoue T, Rüegg MA, Hall MN, Kwiatkowski DJ, Rastaldi MP, Huber TB, Kretzler M, Holzman LB, Wiggins RC, Guan KL. (2011) mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy. (*corresponding) J Clin Invest. 121, 2181-96.
- Narita M, Young A, Arakawa S, Samarajiwa SA, Nakashima T, Yoshida S, Hong S, Berry LS, Reichelt S, Ferreira M, Tavaré S, Inoki K, Shimizu S, Narita M. (2011) Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes. Science. 332, 966-70.
- Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, and Guan KL (2006). TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126, 955-968.
- Inoki K, Corradetti MN, and Guan KL. (2005). Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 37, 19-24.
- Corradetti MN, Inoki K*, Bardeesy N, DePinho RA, and Guan KL*. (2004). Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 18, 1533-1538. (*corresponding)
- Inoki K, Li Y, Xu T, and Guan KL. (2003). Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17, 1829-1834.
- Inoki K, Zhu T, and Guan KL. (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590.
- Inoki K, Li Y, Zhu T, Wu J, and Guan KL. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4, 648-657.
Additional Publications in Pubmed