Author
Rex A. Parker
Other affiliations: Bristol-Myers Squibb
Bio: Rex A. Parker is an academic researcher from Indiana University. The author has contributed to research in topics: Reductase & 7-Dehydrocholesterol reductase. The author has an hindex of 8, co-authored 12 publications receiving 506 citations. Previous affiliations of Rex A. Parker include Bristol-Myers Squibb.
Papers
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TL;DR: Findings are consistent with a model in which both hydroxymethylglutaryl CoA reductase and an associated protein kinase are subject to reversible covalent modulation by phosphorylation-dephosphorylation.
131 citations
131 citations
TL;DR: These new studies support the thesis that liver H MG-CoA reductase is controlled by a bicyclic system in which both HMG- coA reduCTase and HMGCoA reduction kinase are regulated by reversible phosphorylation and are not influenced by CAMP or the specific heat-stable inhibitor of CAMP-dependent protein kinase.
67 citations
TL;DR: Data suggest that a major phosphorylation site of HMG-CoA reductase lies within the "linker" segment joining the membrane spanning and cytoplasmic domains of the native 97-kDa protein.
62 citations
TL;DR: Conversion of native, 97-100 kDa rat liver microsomal HMG CoA reductase to membrane-bound 62 kDa and soluble 52-56 kDa catalytically active forms was catalyzed in vitro by the calcium-dependent, leupeptin- and calpastatin-sensitive protease calpain-II purified from rat liver cytosol.
42 citations
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TL;DR: Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes.
2,755 citations
TL;DR: This review looks at how AMPK integrates stress responses such as exercise as well as nutrient and hormonal signals to control food intake, energy expenditure, and substrate utilization at the whole body level and the possible role of AMPK in multiple common diseases.
Abstract: The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ hete...
1,538 citations
TL;DR: AMP-activated protein kinase and SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress.
Abstract: Mammalian AMP-activated protein kinase and yeast SNF1 protein kinase are the central components of kinase cascades that are highly conserved between animals, fungi, and plants. The AMP-activated protein kinase cascade acts as a metabolic sensor or "fuel gauge" that monitors cellular AMP and ATP levels because it is activated by increases in the AMP:ATP ratio. Once activated, the enzyme switches off ATP-consuming anabolic pathways and switches on ATP-producing catabolic pathways, such as fatty acid oxidation. The SNF1 complex in yeast is activated in response to the stress of glucose deprivation. In this case the intracellular signal or signals have not been identified; however, SNF1 activation is associated with depletion of ATP and elevation of AMP. The SNF1 complex acts primarily by inducing expression of genes required for catabolic pathways that generate glucose, probably by triggering phosphorylation of transcription factors. SNF1-related protein kinases in higher plants are likely to be involved in the response of plant cells to environmental and/or nutritional stress.
1,480 citations
TL;DR: The central hypothesis is that the AMP-activated protein kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress, and protects the cell by switching off ATP-consuming pathways and switching on alternative pathways for ATP generation.
Abstract: A single entity, the AMP-activated protein kinase (AMPK), phosphorylates and regulates in vivo hydroxymethylglutaryl-CoA reductase and acetyl-CoA carboxylase (key regulatory enzymes of sterol synthesis and fatty acid synthesis, respectively), and probably many additional targets. The kinase is activated by high AMP and low ATP via a complex mechanism, which involves allosteric regulation, promotion of phosphorylation by an upstream protein kinase (AMPK kinase), and inhibition of dephosphorylation. This protein-kinase cascade represents a sensitive system, which is activated by cellular stresses that deplete ATP, and thus acts like a cellular fuel gauge. Our central hypothesis is that, when it detects a 'low-fuel' situation, it protects the cell by switching off ATP-consuming pathways (e.g. fatty acid synthesis and sterol synthesis) and switching on alternative pathways for ATP generation (e.g. fatty acid oxidation). Native AMP-activated protein kinase is a heterotrimer consisting of a catalytic alpha subunit, and beta and gamma subunits, which are also essential for activity. All three subunits have homologues in budding yeast, which are components of the SNF1 protein-kinase complex. SNF1 is activated by glucose starvation (which in yeast leads to ATP depletion) and genetic studies have shown that it is involved in derepression of glucose-repressed genes. This raises the intriguing possibility that AMPK may regulate gene expression in mammals. AMPK/SNF1 homologues are found in higher plants, and this protein-kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress.
1,310 citations
TL;DR: There is an integrated network of regulatory pathways, mediated by phosphorylation–dephosphorylation, that allows diverse cellular events to be coordinated by neural and hormonal stimuli, and the evidence that supports this concept is reviewed.
Abstract: Protein phosphorylation is now recognized to be the major general mechanism by which intracellular events in mammalian tissues are controlled by external physiological stimuli However, only recently has the idea that different cellular functions are controlled by common protein kinases and protein phosphatases started to gain widespread acceptance Thus there is an integrated network of regulatory pathways, mediated by phosphorylation-dephosphorylation, that allows diverse cellular events to be coordinated by neural and hormonal stimuli The evidence that supports this concept is reviewed, with emphasis on the role of protein phosphorylation in enzyme regulation
1,065 citations