Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR.

In the past decade, studies of the human tumor suppressor LKB1 have uncovered a novel signaling pathway that links cell metabolism to growth control and cell polarity. LKB1 encodes a serine/threonine kinase that directly phosphorylates and activates AMPK, a …

LKB1 acts a master upstream kinase, directly phosphorylating and activating AMP-activated protein kinase (AMPK) and a family of 12 related kinases that have crucial roles in cell growth,...

Oct 1, 2012 · Numerous studies have reported that LKB1 regulates cell size through activation of AMPK and subsequent inhibition of mTORC1-induced protein synthesis via phosphorylation of TSC2 and/or...

The conditional knockout of Lkb1 in the beta cell compartment of pancreatic islets leads to elevated mTOR activity, increased beta cell mass, and enhanced glucose tolerance. Interestingly, LKB1 controls beta cell size via the mTOR pathway but regulates cell polarity through an mTOR-independent mechanism [32] .

Here we explore the molecular connections between AMPK and mTOR signalling pathways and examine the physiological processes in which AMPK regulation of mTOR is critical for growth or metabolic control.

Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR.

Once activated, LKB1 phosphorylates AMPK, which coordinates activation of catabolic processes—such as glycolysis, Krebs cycle, pentose phosphate pathway, fatty acid oxidation, and autophagy—and inhibition of anabolic processes—such as …

In vitro and in vivo experiments showed the synergistic effect of mTOR inhibition and PI3K inhibition in LKB1-mutant NSCLC cell lines. The sensitivity to dual inhibition of mTOR and PI3K is higher in LKB1-mutant cell lines than in wild-type cell lines.

Here, we report that LKB1 is required for repression of mTOR under low ATP conditions in cultured cells in an AMPK- and TSC2-dependent manner, and that Lkb1 null MEFs and the hamartomatous gastrointestinal polyps from Lkb1 mutant mice show elevated signaling downstream of mTOR.