Calcium/calmodulin-dependent protein kinase kinase 2: roles in signaling and pathophysiology

J Biol Chem. 2012 Sep 14;287(38):31658-65. doi: 10.1074/jbc.R112.356485. Epub 2012 Jul 9.


Many cellular Ca(2+)-dependent signaling cascades utilize calmodulin (CaM) as the intracellular Ca(2+) receptor. Ca(2+)/CaM binds and activates a plethora of enzymes, including CaM kinases (CaMKs). CaMKK2 is one of the most versatile of the CaMKs and will phosphorylate and activate CaMKI, CaMKIV, and AMP-activated protein kinase. Cell expression of CaMKK2 is limited, yet CaMKK2 is involved in regulating many important physiological and pathophysiological processes, including energy balance, adiposity, glucose homeostasis, hematopoiesis, inflammation, and cancer. Here, we explore known functions of CaMKK2 and discuss its potential as a target for therapeutic intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adipose Tissue / enzymology
  • Adiposity
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism*
  • Female
  • Gene Expression Regulation*
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Inflammation / metabolism
  • Liver / enzymology
  • Macrophages / metabolism
  • Male
  • Mice
  • Neurons / metabolism
  • Phosphorylation
  • Prostatic Neoplasms / enzymology
  • Rats
  • Signal Transduction
  • Tissue Distribution


  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • AMP-Activated Protein Kinases
  • Glucose