Evidence that AMP triggers phosphorylation as well as direct allosteric activation of rat liver AMP‐activated protein kinase

Moore, Frances; Weekes, John; Hardie, D. Grahame

doi:10.1111/j.1432-1033.1991.tb16172.x

Cited by 208 publications

(171 citation statements)

References 27 publications

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“…AMPK has been described to be activated during cellular and environmental stress and regulates energy and metabolic homeostasis of the cell (22,37). AMPK-␣ phosphorylation was detected after 24 h of infection in response to the MC58 and MC58 siaD strains (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

et al. 2007

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To extend our knowledge of target proteins in endothelial cells infected with the meningitis-causing pathogen Neisseria meningitidis, we characterized the interaction between the bacterial and human brain microvascular endothelial cell (HBMEC) monolayers. By use of human cDNA microarrays, transcriptional analysis revealed distinct responses to 4 and 8 h of infection. We also addressed the question of whether the major virulence factor of meningococci, i.e., the capsule, influences the host cell response. Of the 1,493 (at 4 h postinfection) and 1,246 (at 8 h postinfection) genes with altered expression upon bacterial contact, about 49.4% and 45%, respectively, depended on capsule expression. In particular, we identified an increase of expression for genes encoding proteins involved in bacterial adhesion and invasion. High levels of apoptosis-related gene (bad, bak, asp, and immediate-early response gene 1) expression could also be detected in infected cells. Further analyses confirmed that HBMECs displayed several hallmarks of apoptosis in response to N. meningitidis infection, namely, phosphatidylserine translocation and activation of caspase 3 and AMP-activated protein kinase ␣. Moreover, several differentially regulated genes not previously known to respond to meningococcal infection were identified. Of these, genes encoding cell adhesion proteins (CD44, CD98, and CD99), genes involved in downstream signaling of integrins (integrin-linked kinase, mitogen-activated protein kinase kinase 1, and mitogen-activated protein kinase kinase kinase 10) as well as negative regulators of these pathways (dualspecificity phosphatases 1, 5, and 14 and G protein pathway suppressor 2), and genes involved in cytoskeleton reorganization (those encoding Arp2/3, p34-arc, actinin alpha 1, vasodilatator-stimulated protein, and Wiskott-Aldrich syndrome protein) were the most prominent. This global transcriptional analysis creates a new platform for further molecular and cellular analysis of the interaction between N. meningitidis and target cells.

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Section: Resultsmentioning

confidence: 99%

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

et al. 2007

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“…AMPK regulates the relative subcellular localization of HuR, probably phosphorylating an additional, as yet unidentified target (Moore et al, 1991;Davies et al, 1995;Salt et al, 1998). Intriguingly, the HuR-associated proteins SETa, SETb, and PP32, by inhibiting protein phosphatase 2A, which in turn would allow active AMPK to elicit downstream effects, could help retain HuR in the nucleus (Wang et al, 2002).…”

Section: Hurmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

294

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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“…AMPKa can also be phosphorylated by calcium/calmodulin-dependent protein kinase kinase, which is triggered through influx of calcium ( Figure 2) (Hawley et al, 1995). The phosphorylation of AMPKa is reversed by the phosphatases PP2A and PP2C (Figure 2) (Moore et al, 1991).…”

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confidence: 99%

The long and winding road to rational treatment of cancer associated with LKB1/AMPK/TSC/mTORC1 signaling

et al. 2011

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The liver kinase B1 (LKB1)/adenosine mono-phosphateactivated protein kinase (AMPK)/tuberous sclerosis complex (TSC)/mammalian target of rapamycin (mTOR) complex (mTORC1) cassette constitutes a canonical signaling pathway that integrates information on the metabolic and nutrient status and translates this into regulation of cell growth. Alterations in this pathway are associated with a wide variety of cancers and hereditary hamartoma syndromes, diseases in which hyperactivation of mTORC1 has been described. Specific mTORC1 inhibitors have been developed for clinical use, and these drugs have been anticipated to provide efficient treatment for these diseases. In the present review, we provide an overview of the metabolic LKB1/AMPK/TSC/mTORC1 pathway, describe how its aberrant signaling associates with cancer development, and indicate the difficulties encountered when biochemical data are extrapolated to provide avenues for rational treatment of disease when targeting this signaling pathway. A careful examination of preclinical and clinical studies performed with rapamycin or derivatives thereof shows that although results are encouraging, we are only half way in the long and winding road to design rationale treatment targeted at the LKB1/ AMPK/TSC/mTORC1 pathway. Inherited cancer syndromes associated with this pathway such as the PeutzJeghers syndrome and TSC, provide perfect models to study the relationship between genetics and disease phenotype, and to delineate the complexities that underlie translation of biochemical and genetical information to clinical management, and thus provide important clues for devising novel rational medicine for cancerous diseases in general.

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Evidence that AMP triggers phosphorylation as well as direct allosteric activation of rat liver AMP‐activated protein kinase

Cited by 208 publications

References 27 publications

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

The long and winding road to rational treatment of cancer associated with LKB1/AMPK/TSC/mTORC1 signaling

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