Fig. 1: The CaMKK2 signalling pathway in the brain.
From: CaMKK2 as an emerging treatment target for bipolar disorder
CaMKK2 is activated endogenously by voltage-gated Ca2+-channels (Cav1.2), in addition to neurotransmitter and hormone receptors that increase intracellular Ca2+ and cause accumulation of the Ca2+-calmodulin (Ca2+-CaM) complex. It can also be activated exogenously by the mood-stabiliser drug, lithium (Li+). Conversely, CaMKK2 is inhibited by CDK5 and GSK3, as well as by hormones that stimulate PKA signalling such as glucagon-like peptide-1 (GLP-1). Activated CaMKK2 directly phosphorylates three known downstream effectors (CaMK1, CaMK4 and AMPK) through which it regulates a range of neuronal and metabolic processes that support brain function.
