AMP-activated protein kinase in skeletal muscle: from structure and localization to its role as a master regulator of cellular metabolism.
The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include the following: (1) the structural components of the three AMPK subunits (i.e. AMPKalpha, beta, and gamma), and their differential localization in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-beta-activated kinase 1 (TAK1); (3) the pharmacological agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle.
Witczak
C A
CA
Metabolism Section, Joslin Diabetes Center, Research Division, 1 Joslin Pl, Boston, MA 02215, USA.
Sharoff
C G
CG
Goodyear
L J
LJ
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D040461:Gene Components; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D005947:Glucose; D020930:MAP Kinase Kinase Kinases; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D000099151:MAP Kinase Kinase Kinase 7; C109790:STK11 protein, human