PMID- 10642499
OWN - NLM
STAT- MEDLINE
DCOM- 20000323
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 345 Pt 3
DP  - 2000 Feb 1
TI  - The regulation of AMP-activated protein kinase by phosphorylation.
PG  - 437-43
AB  - The AMP-activated protein kinase (AMPK) cascade is activated by an increase in
      the AMP/ATP ratio within the cell. AMPK is regulated allosterically by AMP and by
      reversible phosphorylation. Threonine-172 within the catalytic subunit (alpha) of
      AMPK (Thr(172)) was identified as the major site phosphorylated by the
      AMP-activated protein kinase kinase (AMPKK) in vitro. We have used site-directed 
      mutagenesis to study the role of phosphorylation of Thr(172) on AMPK activity.
      Mutation of Thr(172) to an aspartic acid residue (T172D) in either alpha1 or
      alpha2 resulted in a kinase complex with approx. 50% the activity of the
      corresponding wild-type complex. The activity of wild-type AMPK decreased by
      greater than 90% following treatment with protein phosphatases, whereas the
      activity of the T172D mutant complex fell by only 10-15%. Mutation of Thr(172) to
      an alanine residue (T172A) almost completely abolished kinase activity. These
      results indicate that phosphorylation of Thr(172) accounts for most of the
      activation by AMPKK, but that other sites are involved. In support of this we
      have shown that AMPKK phosphorylates at least two other sites on the alpha
      subunit and one site on the beta subunit. Furthermore, we provide evidence that
      phosphorylation of Thr(172) may be involved in the sensitivity of the AMPK
      complex to AMP.
FAU - Stein, S C
AU  - Stein SC
AD  - Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College School of
      Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K.
FAU - Woods, A
AU  - Woods A
FAU - Jones, N A
AU  - Jones NA
FAU - Davison, M D
AU  - Davison MD
FAU - Carling, D
AU  - Carling D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Isoenzymes)
RN  - 0 (Multienzyme Complexes)
RN  - 2ZD004190S (Threonine)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (AMP-activated protein kinase kinase)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Adenosine Monophosphate/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells/metabolism
MH  - Enzyme Activation
MH  - Isoenzymes/metabolism
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Protein-Serine-Threonine Kinases/genetics/*metabolism
MH  - Threonine/metabolism
PMC - PMC1220775
EDAT- 2000/01/22 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/01/22 09:00
PHST- 2000/01/22 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/01/22 09:00 [entrez]
PST - ppublish
SO  - Biochem J. 2000 Feb 1;345 Pt 3:437-43.