Activation AMPK via Receptor tyrosine kinases/Ras/B-Raf
Ras activation
GTPase KRas
Allosteric modulation of H-Ras GTPase
B-Raf
B-Raf is related to retroviral oncogenes and participates in cellular signal transduction. B-Raf domains include the kinase domain - residues 444-721 and Ras-binding domain - residues 153-237. Mutated B-Raf was found in some human cancers[1]. See more in B-RAF with PLX4032.
AMP-activated protein kinase (AMPK) is a nuclear receptor which regulates cellular uptake of glucose, β-oxidation of fatty acids and biogenesis of glucose transporter thus playing a role in cellular energy homeostasis by phosphorylating key proteins. In response to low levels of ATP, AMPK activates energy-producing pathways and inhibits energy-consuming pathways.
AMPK is an important drug target for obesity, type 2 diabetes and cancer. AMPK activity is enhanced during exercise resulting in increased glucose uptake and blood supply in muscles. Stresses like hypoglycemia, anoxia and ischemia produce increase in AMPK levels.
AMPK is a heterotrimer:
is the catalytic subunit and contains .
is a scaffold on which the heterotrimer assembles. There are 2 β subunits. β subunit contains .
detects shifts in AMP:ATP ratio via its 4 cystathionine β synthase (CBS) domains. .[2]
HMG-CoA Reductase is phosphorylated and inactivated by an AMP-activated protein kinase, when the energy charge of the cell is low and AMP concentrations are high.
