RGD Reference Report - AMP-activated protein kinase beta subunit tethers alpha and gamma subunits via its C-terminal sequence (186-270). - Rat Genome Database

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AMP-activated protein kinase beta subunit tethers alpha and gamma subunits via its C-terminal sequence (186-270).

Authors: Iseli, TJ  Walter, M  Van Denderen, BJ  Katsis, F  Witters, LA  Kemp, BE  Michell, BJ  Stapleton, D 
Citation: Iseli TJ, etal., J Biol Chem. 2005 Apr 8;280(14):13395-400. Epub 2005 Jan 28.
RGD ID: 1600470
Pubmed: PMID:15695819   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M412993200   (Journal Full-text)

AMP-activated protein kinase (AMPK) is an important metabolic stress-sensing protein kinase responsible for regulating metabolism in response to changing energy demand and nutrient supply. Mammalian AMPK is a stable alphabetagamma heterotrimer comprising a catalytic alpha and two non-catalytic subunits, beta and gamma. The beta subunit targets AMPK to membranes via an N-terminal myristoyl group and to glycogen via a mid-molecule glycogen-binding domain. Here we find that the conserved C-terminal 85-residue sequence of the beta subunit, beta1-(186-270), is sufficient to form an active AMP-dependent heterotrimer alpha1beta1-(186-270)-gamma1, whereas the 25-residue beta1 C-terminal (246-270) sequence is sufficient to bind gamma1, gamma2, or gamma3 but not the alpha subunit. Deletion of the beta C-terminal Ile-270 precludes betagamma association in the absence of the alpha subunit, but the presence of the alpha subunit or substitution of Ile-270 with Ala or Glu restores betagamma binding. Truncation of the alpha subunit reveals that beta1 binding requires the alpha1-(313-473) sequence. The conserved C-terminal 85-residue sequence of the beta subunit (90% between beta1 and beta2) is the primary alphagamma binding sequence responsible for the formation of the AMPK alphabetagamma heterotrimer.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Prkaa1  (protein kinase AMP-activated catalytic subunit alpha 1)
Prkaa2  (protein kinase AMP-activated catalytic subunit alpha 2)
Prkab1  (protein kinase AMP-activated non-catalytic subunit beta 1)

Objects referenced in this article
Gene Prkab2 protein kinase AMP-activated non-catalytic subunit beta 2 Rattus norvegicus

Additional Information