Abstract:
:We report on a novel method to monitor changes in intracellular cAMP concentration ([cAMP]i) within intact living cells using a chimeric fusion of the catalytic subunit of cAMP-dependent protein kinase to green fluorescent protein (PKAcat-GFP). In stably transfected unstimulated fibroblasts, fusion protein fluorescence is highly concentrated in aggregates throughout the cytoplasm and absent in the nucleus. Elevation of [cAMP]i disperses GFP fluorescence from the cytoplasmic aggregates within minutes. Spot-photobleach measurements show that the rate of exchange of GFP-labeled catalytic subunits at these aggregates increases in proportion to [cAMP]i. For any given stimulus, the response curve for dispersal of GFP fluorescence from aggregates agrees closely with the increase in total [cAMP]i as measured by standard in vitro methods (SPA). The redistribution of fluorescence is completely reversible: reduction of [cAMP]i results in return of fluorescence to the cytoplasmic aggregates. Consistent behaviour of PKAcat-GFP is seen in different cell backgrounds. We demonstrate that PKA Redistribution assays are suitable for measurement of changes in [cAMP]i brought about by both Gs- and Gi-protein-coupled receptor stimulation as well as by inhibition of cAMP phosphodiesterases.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Almholt K,Tullin S,Skyggebjerg O,Scudder K,Thastrup O,Terry Rdoi
10.1016/j.cellsig.2004.01.006subject
Has Abstractpub_date
2004-08-01 00:00:00pages
907-20issue
8eissn
0898-6568issn
1873-3913pii
S089865680400018Xjournal_volume
16pub_type
杂志文章abstract::The roles of protein kinase C (PKC) isoenzymes in the differentiation process of THP-1 cells are investigated. Inhibition of PKC by RO 31-8220 reduces the phagocytosis of latex particles and the release of superoxide, prostaglandin E(2) (PGE(2)), and tumour necrosis factor (TNF)-alpha. The proliferation of THP-1 cells...
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abstract::Epac1 is a cAMP-stimulated guanine exchange factor that activates Rap1. The protein product of the T cell leukemia 1 (TCL1) proto-oncogene binds to Akt enhancing its kinase activity. TCL1 and Epac promote cellular proliferation because of their activating effects on Akt. Employing macrophages, we have studied the mech...
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abstract::Slug, a Snail-related zinc-finger transcription factor implicated in the increased motility of mesenchymal cells during embryonic development and progression of cancer cells towards an invasive phenotype, plays a specific and critical role in the pathogenesis of Bcr-Abl-associated leukemias. Here we report that Slug o...
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abstract::The mechanistic target of rapamycin complex 1 (mTORC1) is a central modulator of inflammation and tumorigenesis in the gastrointestinal tract. Growth factors upregulate mTORC1 via the PI3K/AKT and/or Ras/MAPK signal pathways. Curcumin (CUR), a polyphenol found in turmeric roots (Curcuma longa) can repress mTORC1 kinas...
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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abstract::JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan i...
journal_title:Cellular signalling
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abstract::The mammalian target of rapamycin complex 1(mTORC1) integrates diverse signals to control cell growth, proliferation, survival, and metabolism. Role of reactive oxygen species (ROS) on mTORC1 signaling remains obscure and mechanisms through which ROS modulate mTORC1 are not known.We demonstrate that low doses ROS expo...
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doi:10.1016/j.cellsig.2010.05.015
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journal_title:Cellular signalling
pub_type: 杂志文章
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abstract::We analysed the effects of high glucose in rat1 cells overexpressing insulin receptor. High (25 mM) glucose inhibited insulin-stimulated tyrosine kinase activity completely at insulin concentrations of 1 and 5 ng/ml. Decapeptides modelled on insulin receptor sequences surrounding serines 1035 and 1270 were found to in...
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2014.09.001
更新日期:2014-12-01 00:00:00
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doi:10.1016/j.cellsig.2010.06.007
更新日期:2010-11-01 00:00:00
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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更新日期:1996-03-01 00:00:00
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journal_title:Cellular signalling
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abstract::The cyclin-dependent kinase inhibitors (CKI) interact with cyclin-cdk complexes to arrest mitogen-stimulated transit through the cell cycle, but we and others have recently shown that these molecules can exert permissive effects on cell cycle transit as well. The p53 protein induces transcription of the p21(Waf1/Cip1)...
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2012.08.012
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journal_title:Cellular signalling
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更新日期:2007-06-01 00:00:00
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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