CAMKK2

Description

The CAMKK2 (calcium/calmodulin dependent protein kinase kinase 2) is a protein-coding gene located on chromosome 12.

CAMKK2 (Calcium/calmodulin-dependent protein kinase kinase 2) is an enzyme encoded by the CAMKK2 gene in humans. It belongs to the serine/threonine-specific protein kinase family and the Ca++/calmodulin-dependent protein kinase subfamily. CAMKK2 acts within the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4, enhancing their catalytic activity. This phosphorylation occurs at Thr 177 for CaMK1 and Thr 196 for CaMK4. CAMKK2 regulates the production of neuropeptide Y, an appetite-stimulating hormone, and functions as an AMPK kinase in the hypothalamus. It is also crucial in the development of hyperalgesia and tolerance to opioid analgesic drugs by reducing downstream signaling pathways and downregulating the mu opioid receptor. In mice, inhibiting CAMKK2 reduces appetite and promotes weight loss. CAMKK2 plays diverse roles in various brain regions. In the hippocampus, the CAMKK2/CaMK1 cascade is essential for memory formation by regulating learning-induced structural changes in the neuronal cytoskeleton. Morphological alterations in dendritic spines within the hippocampus, necessary for initiating and maintaining synaptic plasticity in CA1 pyramidal neurons, are the foundation for memory formation.

CAMKK2 is a calcium-dependent protein kinase that plays a crucial role in various cellular processes by participating in a calcium-triggered signaling cascade. Different isoforms of CAMKK2 exhibit distinct functions: Isoforms 1, 2, and 3 are responsible for phosphorylating CAMK1 and CAMK4, while isoform 3 additionally phosphorylates CAMK1D. Isoforms 4, 5, and 6, lacking a portion of the calmodulin-binding domain, are inactive. CAMKK2 efficiently phosphorylates the 5'-AMP-activated protein kinase (AMPK) trimer, including the complex composed of PRKAA1, PRKAB1, and PRKAG1. This phosphorylation is triggered by calcium signals. CAMKK2 is thought to be involved in the hippocampal activation of CREB1 and may contribute to neurite growth. Notably, isoform 3 promotes neurite elongation, whereas isoform 1 stimulates neurite branching. CAMKK2 interacts with calmodulin.

CAMKK2 is also known as CAMKK, CAMKKB.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing