LKB1 regulates development and the stress response in Dictyostelium

Abstract

The serine/threonine kinase LKB1 is a master kinase that regulates a number of critical events such as cell transformation, polarization, development, stress response, and energy metabolism in metazoa. After multiple unsuccessful attempts of generating Dictyostelium lkb1-null cells, an RNAi-based knockdown approach proved effective. Depletion of lkb1 with a knockdown construct displayed severe reduction in prespore cell differentiation and precocious induction of prestalk cells, which were reminiscent of cells lacking GSK3. Similarly to gsk3− cells, lkb1 depleted cells displayed lower GSK3 activity than wild type cells during development and compromised cAMP-mediated inhibition of the DIF-1 mediated ecmB induction. In response to stress insult, the kinase activity of LKB1, but not that of GSK3, increased. Therefore, LKB1 positively functions at the upstream of GSK3 during development and responds to stress insults independently from GSK3.

Curcumin treatment enhances the effect of exercise on mitochondrial biogenesis in skeletal muscle by increasing cAMP levels

“…ACCEPTED MANUSCRIPT 19 muscles would be superior to that of resveratrol and directed through the regulation of mitochondrial biogenesis. In this study, curcumin treatment increased the levels of markers of mitochondrial biogenesis in skeletal muscle in a similar fashion to combination treatment with endurance training, suggesting that curcumin treatment together with exercise plays a role in the regulation of mitochondrial biogenesis in skeletal muscle.…”

“…Protein kinase A (PKA), also known as cAMP-dependent enzyme, is a well-studied, downstream effector of cAMP and is activated only in the presence of cAMP. Activated PKA phosphorylates a number of other proteins including cAMP response element binding protein (CREB) and liver kinase B1 (LKB-1), which induces PGC-1α to regulate mitochondria biogenesis ( [18,19]. Previous studies have provided evidence that exercise, including swimming and running increase cAMP levels in skeletal muscle and myocardium [20] and the mitochondrial biogenesis seen after exercise may be attributable to this increase.…”

Protein kinase LKB1 promotes RAB7-mediated neuropilin-1 degradation to inhibit angiogenesis

“…Among the diverse functions of LKB1 are the regulation of hematopoietic stem cell survival, mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK) (1)(2)(3)(4). As a stress-responsive gene (5), LKB1 displays varying effects under cell stress conditions, such as serum deprivation or hypoxia. The essential functions of LKB1 are best demonstrated by the fact that global Lkb1 knockout is embryonically lethal in mice (6).…”

‘Biogeneric’ developmental processes: drivers of major transitions in animal evolution

“…This protein also exists in animals, where it mediates A/B-related cell shape changes during embryogenesis [37]. In regulating cell polarity, Mo25 operates in conjunction with the enzyme Lkb1 [38], which not only has a homologue in brewers yeast, but also in the more distantly related social amoebae Dictyostelium discoideum, where it is also involved in morphogenesis [39].…”