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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2011-4-4
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pubmed:abstractText |
Activation of G-protein-coupled receptors (GPCRs) mobilizes compartmentalized pulses of cyclic AMP. The main cellular effector of cAMP is protein kinase A (PKA), which is assembled as an inactive holoenzyme consisting of two regulatory (R) and two catalytic (PKAc) subunits. cAMP binding to R subunits dissociates the holoenzyme and releases the catalytic moiety, which phosphorylates a wide array of cellular proteins. Reassociation of PKAc and R components terminates the signal. Here we report that the RING ligase praja2 controls the stability of mammalian R subunits. Praja2 forms a stable complex with, and is phosphorylated by, PKA. Rising cAMP levels promote praja2-mediated ubiquitylation and subsequent proteolysis of compartmentalized R subunits, leading to sustained substrate phosphorylation by the activated kinase. Praja2 is required for efficient nuclear cAMP signalling and for PKA-mediated long-term memory. Thus, praja2 regulates the total concentration of R subunits, tuning the strength and duration of PKA signal output in response to cAMP.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1476-4679
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pubmed:author |
pubmed-author:AnnunziatoLucioL,
pubmed-author:CarlucciAnnalisaA,
pubmed-author:CuomoOrnellaO,
pubmed-author:FelicielloAntonioA,
pubmed-author:GarbiCorradoC,
pubmed-author:LignittoLucaL,
pubmed-author:NisticòRobertR,
pubmed-author:SavoiaClaudiaC,
pubmed-author:ScorzielloAntonellaA,
pubmed-author:SepeMariaM,
pubmed-author:StefanEduardE
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pubmed:copyrightInfo |
© 2011 Macmillan Publishers Limited. All rights reserved
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pubmed:issnType |
Electronic
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
412-22
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pubmed:dateRevised |
2011-9-20
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pubmed:meshHeading |
pubmed-meshheading:21423175-A Kinase Anchor Proteins,
pubmed-meshheading:21423175-Animals,
pubmed-meshheading:21423175-Cell Line, Tumor,
pubmed-meshheading:21423175-Cyclic AMP,
pubmed-meshheading:21423175-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:21423175-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:21423175-DNA-Binding Proteins,
pubmed-meshheading:21423175-Enzyme Activation,
pubmed-meshheading:21423175-Enzyme Stability,
pubmed-meshheading:21423175-HEK293 Cells,
pubmed-meshheading:21423175-Humans,
pubmed-meshheading:21423175-Long-Term Potentiation,
pubmed-meshheading:21423175-Mice,
pubmed-meshheading:21423175-Neuroblastoma,
pubmed-meshheading:21423175-Neurons,
pubmed-meshheading:21423175-Protein Subunits,
pubmed-meshheading:21423175-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:21423175-Rats,
pubmed-meshheading:21423175-Recombinant Fusion Proteins,
pubmed-meshheading:21423175-Signal Transduction,
pubmed-meshheading:21423175-Two-Hybrid System Techniques,
pubmed-meshheading:21423175-Ubiquitin-Protein Ligases
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pubmed:year |
2011
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pubmed:articleTitle |
Control of PKA stability and signalling by the RING ligase praja2.
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pubmed:affiliation |
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Universitá Federico II, 80131 Naples, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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