Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase.
The 5'-AMP-activated protein kinase is responsible for the regulation of fatty acid synthesis by phosphorylation and inactivation of acetyl-CoA carboxylase. The porcine liver 5'-AMP-activated protein kinase 63-kDa catalytic subunit co-purifies 14,000-fold with a 38- and 40-kDa protein (Mitchelhill, K.I. et al. (1994) J. Biol. Chem. 269, 2361-2364). The 63-kDa subunit is homologous to the Saccharomyces cerevisiae Snf1 protein kinase, which regulates gene expression during glucose derepression. Peptide amino acid and polymerase chain reaction-derived partial cDNA sequences of both the pig and rat liver enzymes show that the 38-kDa protein is homologous to Snf4p (CAT3) and that the 40-kDa protein is homologous to the Sip1p/Spm/GAL83 family of Snf1p interacting proteins. Sucrose density gradient and cross-linking experiments with purified 5'-AMP-activated protein kinase suggest that both the 38- and 40-kDa proteins associate tightly with the 63-kDa catalytic polypeptide in either a heterotrimeric complex or in dimeric complexes. The 40-kDa subunit is autophosphorylated within the 63-kDa subunit complex. The sequence relationships between the mammalian 5'-AMP-activated protein kinase and yeast Snf1p extend to the subunit proteins consistent with conservation of the functional roles of these polypeptides in cellular regulation by this family of metabolite-sensing protein kinases.
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
D
D
Stapleton
G
G
Gao
B J
BJ
Michell
J
J
Widmer
K
K
Mitchelhill
T
T
Teh
C M
CM
House
L A
LA
Witters
B E
BE
Kemp
D055372:AMP-Activated Protein Kinases; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D018076:DNA, Complementary; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D013552:Swine
D018076:DNA, Complementary; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D011494:Protein Kinases; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases