ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase

• DOI: 10.1016/j.cmet.2011.09.009
• Publication Date: 2011-10-24T18:43:28Z
• Authors: Faith V. Mayer; Richard Heath; Elizabeth Underwood; Matthew J. Sanders; David Carmena; Rhonda R. McCartney; Fiona C. Leiper; Bing Xiao; Chun Jing; Philip A. Walker; Lesley F. Haire; Roksana Ogrodowicz; Stephen R. Martin; Martin C. Schmidt; Steven J. Gamblin; David Carling
• Keywords: Dephosphorylation; AMP-Activated Protein Kinase; c-Raf; Casein kinase 2

The SNF1 protein kinase complex plays an essential role in regulating gene expression response to the level of extracellular glucose budding yeast. shares structural and functional similarities with mammalian AMP-activated kinase. Both kinases are activated by phosphorylation on a threonine residue within activation loop segment catalytic subunit. Here we show that ADP is long-sought metabolite activates limitation protecting enzyme against dephosphorylation Glc7, its physiologically relevant phosphatase. We also regulatory subunit has two binding sites. tighter site binds AMP, ADP, ATP competitively NADH, whereas weaker does not bind but responsible for mediating protective effect dephosphorylation. Mutagenesis experiments suggest general mechanism which protects strongly conserved between AMPK.