154 results found
Beri RK, Marley AE, See CG, et al., 1994, Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase., FEBS Lett, Vol: 356, Pages: 117-121, ISSN: 0014-5793
A cDNA encoding rat liver AMP-activated protein kinase (AMPK) was used to isolate human skeletal muscle AMPK cDNA clones. Human AMPK cDNA is more than 90% homologous to the rat sequence and predicts a protein of molecular mass 62.3 kDa, which closely agrees with the mass observed in Western blots of human tissues. AMPK antibodies were also shown to immunoprecipitate AMPK from human liver extracts. A cDNA probe was used to identify a 9.5kb transcript in several human tissues and to isolate human genomic clones. PCR mapping of rodent/human hybrid cell lines localised the human AMPK gene to chromosome 1, and fluorescent in situ hybridisation with a human genomic clone was used to sub-localise the human AMPK gene to 1p31.
Woods A, Munday MR, Scott J, et al., 1994, Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo., J Biol Chem, Vol: 269, Pages: 19509-19515, ISSN: 0021-9258
The product of the SNF1 gene is a protein kinase whose activity is essential for transcriptional activation of glucose repressed genes in Saccharomyces cerevisiae. We have cloned a mammalian AMP-activated protein kinase (AMPK) that is 46% identical to the deduced amino acid sequence of SNF1 (Carling, D., Aguan, K., Woods, A., Verhoeven, A.J.M., Beri, R., Brennan, C.H., Sidebottom, C., Davison, M.D., and Scott, J. (1994) J. Biol. Chem. 269, 11442-11448). Mammalian AMPK plays a major role in the control of lipid metabolism and phosphorylating, thereby inactivating both acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase, key regulatory enzymes in the synthesis of fatty acids and cholesterol, respectively. We present evidence indicating that, in common with its mammalian homologue, SNF1 forms part of a protein kinase cascade. SNF1 is inactivated in vitro by treatment with protein phosphatase 2A and can be reactivated using a partially purified preparation of mammalian AMPK kinase. SNF1 undergoes a time-dependent increase in activity during growth in glucose-derepressing conditions, providing the first evidence that SNF1 activity is regulated by the level of available glucose. In wild-type yeast, but not in a snf1 deletion mutant, acetyl-CoA carboxylase shows a reciprocal change in activity compared with SNF1 under glucose derepressing conditions, indicating that SNF1 regulates acetyl-CoA carboxylase in vivo. These results suggest that, in addition to their structural similarity, the role of SNF1 and AMPK in the regulation of fatty acid synthesis has been highly conserved throughout evolution.
DAVIES SP, HAWLEY SA, WOODS A, et al., 1994, PURIFICATION OF THE AMP-ACTIVATED PROTEIN-KINASE ON ATP-GAMMA-SEPHAROSE AND ANALYSIS OF ITS SUBUNIT STRUCTURE, EUROPEAN JOURNAL OF BIOCHEMISTRY, Vol: 223, Pages: 351-357, ISSN: 0014-2956
Carling D, Aguan K, Woods A, et al., 1994, Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism., J Biol Chem, Vol: 269, Pages: 11442-11448, ISSN: 0021-9258
In mammals, an AMP-activated protein kinase (AMPK) phosphorylates both acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro and has been proposed to play a major role in the regulation of lipid metabolism in vivo. We report here the primary sequence of rat AMPK and show that antibodies raised against synthetic peptides based on the deduced sequence of AMPK immunoprecipitate AMPK activity from rat liver extracts. AMPK has a remarkable degree of sequence identity to the proteins encoded by the yeast SNF1 gene and the plant RKIN1 gene. SNF1 protein kinase activity is essential for release of genes from glucose repression in Saccharomyces cerevisiae. Expression of cRKIN1 in yeast snf1 mutants restores SNF1 function. These results indicate that AMPK, SNF1, and RKIN1 form part of a family of protein kinases that have been highly conserved throughout evolution. Our results suggest that AMPK may be involved in the regulation of a wide range of metabolic pathways.
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