Inaugural Article: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress

By R. J. Shaw. 2004

1,868 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/f8d31d014855df08f8e742bdf874ab5001f5b4b0

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. David M. Sabatini
2. K. Guan
3. M. Laplante
4. B. Manning
5. R. Shaw
6. Young Chul Kim
7. K. Inoki
8. Michael Pollak

Citations in the corpus

• Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression (2004, background): “Thus, LKB1 influences the ability of energy status to modulate mTOR function, and as a result, its inactivation results in aberrrantly high mTOR-dependent signaling even under low-energy conditions (Shaw et al., 2004).”
• Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. (2007, background): “In addition to its reported activation in response to acute decreases in intracellular AMP/ATP ratios, AMPK has also been shown to be directly activated via phosphorylation, at residue Thr-172, by the upstream tumor suppressor LKB1 (38).”
• Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. (2006, background): “Interestingly, several cancer cell lines, but not the LKB1 / HeLa cell line (10), were growth inhibited.”
• The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon (2011, unknown): “AMPK (5’-adenosine monophosphate-activated protein kinase) is a metabolic sensor activated by falling ATP and/ or rising AMP levels (Shaw et al., 2004).”
• AMPK is a negative regulator of the Warburg Effect and suppresses tumor growth in vivo (2012, background): “Consistent with past work (Inoki et al., 2003; Liu et al., 2006; Shaw et al., 2004a), we find that AMPK functions to downregulate TORC1 activity specifically under conditions of energetic stress, when it is desirable to suppress ATP-consuming processes such as mRNA translation.”
• AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. (2011, background): “The major upstream kinase phosphorylating Thr 172, and thus activating AMPK, in most mammalian cells is a complex between the tumor suppressor kinase LKB1 and two accessory subunits, STRAD and MO25 (Hawley et al. 2003; Woods et al. 2003; Shaw et al. 2004).”
• Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling. (2008, background): “In addition to inhibitory phosphorylation, TSC2 is activated by phosphorylation through the LKB1/AMPK pathway, which contributes to mTORC1 inhibition in the setting of energy deprivation and long-term hypoxic stress (Corradetti et al. 2004; Shaw et al. 2004; Liu et al. 2006).”