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AMP‐activated protein kinase and the regulation of energy metabolism
Author(s) -
Carling David
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a206-d
Subject(s) - ampk , protein kinase a , amp activated protein kinase , heterotrimeric g protein , microbiology and biotechnology , kinase , chemistry , protein subunit , biology , biochemistry , signal transduction , g protein , gene
AMP‐activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining energy balance within the cell. In addition, AMPK plays a role in the central regulation of feeding. This places AMPK in a pivotal position for regulating whole body energy metabolism. AMPK is a heterotrimeric complex consisting of an α catalytic subunit and two regulatory subunits (β and γ). The γ subunit contains four copies of a protein module termed a CBS domain, and these domains appear to play a role in the allosteric regulation of AMPK by nucleotides. Mutations in the γ2 subunit cause cardiac hypertrophy and arrhythmia in humans, and this is associated with cardiac glycogen accumulation. Interestingly, the β subunit contains a glycogen‐binding domain. AMPK is activated by phosphorylation and studies have identified LKB1 and calcium calmodulin dependent protein kinase kinase β as upstream kinases in the AMPK cascade. Inactivating mutations in LKB1 lead to a hereditary form of cancer termed Peutz‐Jeghers syndrome, raising the possibility that AMPK may provide a link in human diseases whose underlying cause is due to defects in energy metabolism. I will discuss the evidence implicating AMPK as a key regulator of energy metabolism.