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PMID:14511394

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Citation

Hawley, SA, Boudeau, J, Reid, JL, Mustard, KJ, Udd, L, Mäkelä, TP, Alessi, DR and Hardie, DG (2003) Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2:28

Abstract

The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that acts as a 'metabolic master switch' and inhibits cell proliferation. Activation requires phosphorylation of Thr172 of AMPK within the activation loop by upstream kinases (AMPKKs) that have not been identified. Recently, we identified three related protein kinases acting upstream of the yeast homolog of AMPK. Although they do not have obvious mammalian homologs, they are related to LKB1, a tumor suppressor that is mutated in the human Peutz-Jeghers cancer syndrome. We recently showed that LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta.

Links

PubMed PMC333410 Online version:10.1186/1475-4924-2-28

Keywords

AMP-Activated Protein Kinases; Adaptor Proteins, Signal Transducing/metabolism; Adaptor Proteins, Vesicular Transport/metabolism; Animals; Catalytic Domain; Cell Line; Cell Line, Tumor; Cell-Free System; Embryo, Mammalian/cytology; Enzyme Activation/physiology; Fibroblasts/enzymology; Fibroblasts/metabolism; Genes, Tumor Suppressor; HeLa Cells/chemistry; HeLa Cells/enzymology; HeLa Cells/metabolism; HeLa Cells/pathology; Humans; Immunoprecipitation/methods; Kidney/chemistry; Kidney/cytology; Kidney/embryology; Kidney/enzymology; Liver/enzymology; Mice; Multienzyme Complexes/metabolism; Multienzyme Complexes/physiology; Multiprotein Complexes/metabolism; Multiprotein Complexes/physiology; Protein Kinases/chemistry; Protein Kinases/metabolism; Protein Subunits/metabolism; Protein-Serine-Threonine Kinases/biosynthesis; Protein-Serine-Threonine Kinases/chemistry; Protein-Serine-Threonine Kinases/deficiency; Protein-Serine-Threonine Kinases/metabolism; Protein-Serine-Threonine Kinases/physiology; Rats; Recombinant Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:A0A0G2JZH0

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:D3ZJ77

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:STK11

enables

GO:0044877: protein-containing complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:STK11

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:STK11

enables

GO:0044877: protein-containing complex binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:1306390
RGD:727905

F

Seeded From UniProt

complete

RAT:STK11

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:AAPK1

enables

GO:0044877: protein-containing complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:AAKG1

enables

GO:0044877: protein-containing complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:AAKG1

contributes_to

GO:0004679: AMP-activated protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:AAKG1

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:AAKB1

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:AAPK2

enables

GO:0044877: protein-containing complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:AAPK2

enables

GO:0004679: AMP-activated protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:AAPK2

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:STRAA

enables

GO:0044877: protein-containing complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:STRAA

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:STRAA

contributes_to

GO:0004674: protein serine/threonine kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:STRAA

involved_in

GO:0032147: activation of protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:AAPK1

involved_in

GO:0051291: protein heterooligomerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:AAPK1

part_of

GO:0032991: protein-containing complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:AAPK1

enables

GO:0004679: AMP-activated protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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