Disease relevance of lkb1

• Thus, Drosophila and human LKB1 may be functional homologues, suggesting that loss of cell polarity may contribute to tumour formation in individuals with Peutz-Jeghers syndrome [1].
• Consistently, LKB1-null mutant was defective in embryonic apoptosis and displayed a drastic hyperplasia in the central nervous system; these phenotypes were fully rescued by ectopic JNK activation as well as wild-type LKB1 expression [2].

High impact information on lkb1

• Here we show that the Drosophila par-4 homologue, lkb1, is required for the early A-P polarity of the oocyte, and for the repolarization of the oocyte cytoskeleton that defines the embryonic A-P axis [1].
• We show that the level of AMPK phosphorylation increases during calcium-induced tight junction assembly and cell polarization and that this increase depends on the kinase activity of LKB1 [3].
• Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo [2].
• Furthermore, inhibition of LKB1 resulted in epithelial morphogenesis failure, which was associated with a decrease in JNK activity [2].
• JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila [2].

Biological context of lkb1

• This screen identified the serine/threonine kinase LKB1, which is involved in the regulation of cell cycle progression and polarity [4].
• Here, we showed that Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis, without affecting cell size and cell cycle progression [2].

References