Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and with protein fractions of rat liver cytosol

Beg, Zafarul H.; Allmann, David W.; Gibson, D. M.

doi:10.1016/0006-291x(73)91137-6

Cited by 298 publications

(99 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 1973 Beg and coworkers reported that a microsomal preparation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), a key regulatory enzyme of cholesterol biosynthesis, was inactivated in a time-dependent manner by incubation with MgATP and a cytosolic fraction (1). The same phenomenon was observed in microsomes from human fibroblasts, where evidence was presented that both ADP and ATP were required (5).…”

Section: Early History Of Mammalian Amp-activated Protein Kinasementioning

confidence: 53%

“…With hindsight it is now possible to date the first experimental observations of AMP-activated protein kinase (AMPK) to two independent studies in 1973 (1,2), although it was to be 14 years before it was realized that the phenomena studied were related (3) and 16 years before the kinase was given the name by which it is known today (4). In 1973 Beg and coworkers reported that a microsomal preparation of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), a key regulatory enzyme of cholesterol biosynthesis, was inactivated in a time-dependent manner by incubation with MgATP and a cytosolic fraction (1).…”

Section: Early History Of Mammalian Amp-activated Protein Kinasementioning

confidence: 99%

See 1 more Smart Citation

THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?

Hardie

Carling

Carlson

1998

Annu. Rev. Biochem.

1,362

1,347

View full text Add to dashboard Cite

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.

show abstract

Section: Early History Of Mammalian Amp-activated Protein Kinasementioning

confidence: 53%

Section: Early History Of Mammalian Amp-activated Protein Kinasementioning

confidence: 99%

THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?

Hardie

Carling

Carlson

1998

Annu. Rev. Biochem.

1,362

1,347

View full text Add to dashboard Cite

show abstract

“…Adenosine monophosphate (AMP) -activated protein kinase is a protein kinase originally discovered via its ability to inactivate two key enzymes of lipid biosynthesis, that is, acetyl-CoA carboxylase (Carlson and Kim 1973) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (Beg et al 1973). Both activities were shown to be allosterically activated by AMP (Yeh et al 1980;Ferrer et al 1985), but it was not realized that they were catalyzed by the same protein kinase until the author's laboratory provided evidence for this (Carling et al 1987).…”

mentioning

confidence: 99%

Adenosine Monophosphate-Activated Protein Kinase: A Central Regulator of Metabolism with Roles in Diabetes, Cancer, and Viral Infection

Hardie¹

2011

Cold Spring Harbor Symposia on Quantitative Biology

View full text Add to dashboard Cite

Adenosine monophosphate -activated protein kinase (AMPK) is a cellular energy sensor activated by metabolic stresses that inhibit catabolic ATP production or accelerate ATP consumption. Once activated, AMPK switches on catabolic pathways, generating ATP, while inhibiting cell growth and proliferation, thus promoting energy homeostasis. AMPK is activated by the antidiabetic drug metformin, and by many natural products including "nutraceuticals" and compounds used in traditional medicines. Most of these xenobiotics activate AMPK by inhibiting mitochondrial ATP production. AMPK activation by metabolic stress requires the upstream kinase, LKB1, whose tumor suppressor effects may be largely mediated by AMPK. However, many tumor cells appear to have developed mechanisms to reduce AMPK activation and thus escape its growthrestraining effects. A similar phenomenon occurs during viral infection. If we can establish how down-regulation occurs in tumors and virus-infected cells, there may be therapeutic avenues to reverse these effects.

show abstract

“…First described 35 years ago (Beg et al, 1973;Carlson and Kim, 1973), and named in 1987 (Carling et al, 1987), mammalian AMPK is homologous to the yeast sucrose non-fermenting (Snf1) gene product, involved in substrate selection in S. cerevisiae (Celenza and Carlson, 1984), to the plant SNF-1 related kinase, SnRK (Alderson et al, 1991) and to C. elegans AAK-1 and AAK-2 (Apfeld et al, 2004). Considered principally as an "emergency response" enzyme in mammals, activated only during severe metabolic stress during which intracellular 5'AMP levels were raised as those of ATP fell, AMPK was substantially ignored by all but a very few groups for the next twenty years (Stapleton et al, 1996;Hardie et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The AMP-regulated kinase family: Enigmatic targets for diabetes therapy

Rutter

Leclerc

2009

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Please cite this article as: Rutter, G.A., Leclerc, I., The AMP-regulated kinase family: enigmatic targets for diabetes therapy, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Pt 1):1-16, 2003). In the subsequent five years, dramatic strides have taken place in our understanding of the role of AMPK in the control of whole body metabolic homeostasis, the regulation of the enzyme by upstream kinases, and its molecular structure.These new studies and earlier work arguably propel AMPK, and perhaps related family members into a "super league" of potential therapeutic targets for maladies including diabetes, cancer, heart disease, and obesity. Here we survey some of these recent advances, focussing on the role of this and related enzymes in the control of pancreatic β-cell function and glucose homeostasis.

show abstract

Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and with protein fractions of rat liver cytosol

Cited by 298 publications

References 11 publications

THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?

THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?

Adenosine Monophosphate-Activated Protein Kinase: A Central Regulator of Metabolism with Roles in Diabetes, Cancer, and Viral Infection

The AMP-regulated kinase family: Enigmatic targets for diabetes therapy

Contact Info

Product

Resources

About