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Your search keyword '"van Denderen, Bryce J. W."' showing total 2 results
Start Over Author "van Denderen, Bryce J. W." Publisher cell press
2 results on '"van Denderen, Bryce J. W."'

1. Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling.

Author

Steinberg GR, Michell BJ, van Denderen BJ, Watt MJ, Carey AL, Fam BC, Andrikopoulos S, Proietto J, Görgün CZ, Carling D, Hotamisligil GS, Febbraio MA, Kay TW, and Kemp BE

Subjects
Adenylate Kinase genetics, Animals, Lipid Metabolism genetics, Mice, Mice, Mutant Strains, Muscle, Skeletal pathology, Obesity genetics, Obesity pathology, Oxidation-Reduction, Phosphoprotein Phosphatases genetics, Phosphoprotein Phosphatases metabolism, Protein Phosphatase 2C, Receptors, Tumor Necrosis Factor, Type I deficiency, Receptors, Tumor Necrosis Factor, Type I metabolism, Receptors, Tumor Necrosis Factor, Type II genetics, Receptors, Tumor Necrosis Factor, Type II metabolism, Tumor Necrosis Factor-alpha genetics, Adenylate Kinase biosynthesis, Insulin Resistance genetics, Muscle, Skeletal enzymology, Obesity enzymology, Signal Transduction genetics, Tumor Necrosis Factor-alpha metabolism
Abstract

Elevated levels of tumor necrosis factor (TNFalpha) are implicated in the development of insulin resistance, but the mechanisms mediating these chronic effects are not completely understood. We demonstrate that TNFalpha signaling through TNF receptor (TNFR) 1 suppresses AMPK activity via transcriptional upregulation of protein phosphatase 2C (PP2C). This in turn reduces ACC phosphorylation, suppressing fatty-acid oxidation, increasing intramuscular diacylglycerol accumulation, and causing insulin resistance in skeletal muscle, effects observed both in vitro and in vivo. Importantly even at pathologically elevated levels of TNFalpha observed in obesity, the suppressive effects of TNFalpha on AMPK signaling are reversed in mice null for both TNFR1 and 2 or following treatment with a TNFalpha neutralizing antibody. Our data demonstrate that AMPK is an important TNFalpha signaling target and is a contributing factor to the suppression of fatty-acid oxidation and the development of lipid-induced insulin resistance in obesity.

Published
2006
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2. Structural basis for glycogen recognition by AMP-activated protein kinase.

Author

Polekhina G, Gupta A, van Denderen BJ, Feil SC, Kemp BE, Stapleton D, and Parker MW

Subjects
AMP-Activated Protein Kinases, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Carbohydrate Conformation, Catalytic Domain, Crystallography, X-Ray, Glucans pharmacology, Glucose chemistry, Glycogen chemistry, Glycogen genetics, Leucine chemistry, Liver enzymology, Models, Molecular, Molecular Sequence Data, Multienzyme Complexes chemistry, Multienzyme Complexes isolation & purification, Mutagenesis, Site-Directed, Mutation, Oligosaccharides pharmacology, Protein Binding, Protein Serine-Threonine Kinases chemistry, Protein Serine-Threonine Kinases isolation & purification, Protein Structure, Tertiary, Protein Subunits chemistry, Protein Subunits metabolism, Rats, Sequence Homology, Amino Acid, Spectrum Analysis, Raman, Tryptophan chemistry, Water chemistry, beta-Cyclodextrins chemistry, beta-Cyclodextrins metabolism, beta-Cyclodextrins pharmacology, Glycogen metabolism, Multienzyme Complexes metabolism, Protein Serine-Threonine Kinases metabolism
Abstract

AMP-activated protein kinase (AMPK) coordinates cellular metabolism in response to energy demand as well as to a variety of stimuli. The AMPK beta subunit acts as a scaffold for the alpha catalytic and gamma regulatory subunits and targets the AMPK heterotrimer to glycogen. We have determined the structure of the AMPK beta glycogen binding domain in complex with beta-cyclodextrin. The structure reveals a carbohydrate binding pocket that consolidates all known aspects of carbohydrate binding observed in starch binding domains into one site, with extensive contact between several residues and five glucose units. beta-cyclodextrin is held in a pincer-like grasp with two tryptophan residues cradling two beta-cyclodextrin glucose units and a leucine residue piercing the beta-cyclodextrin ring. Mutation of key beta-cyclodextrin binding residues either partially or completely prevents the glycogen binding domain from binding glycogen. Modeling suggests that this binding pocket enables AMPK to interact with glycogen anywhere across the carbohydrate's helical surface.

Published
2005
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