AMPK regulates the S6K1 pathway and protein synthesis in avian QM7 myoblasts

摘要

The AMP-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status and a major cellular regulator of lipid and glucose metabolism (Gorton et al., 1994; Hardie and Carling, 1997). AMPK corresponds to a heterotrimetric complex comprising a catalytic alpha subunit and two regulatory beta and gamma subunits; there are several isoforms for each subunit (alpha1, alpha2, beta1, beta2, gamma1, gamma2, gamma3). Binding of AMP to the y subunit of AMPK triggers phosphorylation on threonine 172 of the catalytic alpha subunit by the upstream AMPK kinase called LKB1, resulting in increased enzyme activity. AMPK plays a key role in controlling cell energy metabolism, including the regulation of glucose utilisation, fatty acid oxidation and glycogen metabolism (Carling, 2004). In some models, AMPK can also inhibit protein synthesis via the target of rapamycin (TOR)/p70 S6 Kinase (S6K1) pathway (Hardie, 2005) even if some intriguing observations have recently shown heightened insulin responses of S6K1 following AMPK activation (Longnus et al., 2005).