ArticleThe Journal of biological chemistry2009
Mdm2 directs the ubiquitination of beta-arrestin-sequestered cAMP phosphodiesterase-4D5.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 63 citations in OpenAlex.
- Isoprenaline modified the lipidomic profile and reduced β-oxidation in HL-1 cardiomyocytes:Frontiers in cardiovascular medicine · 2022Article
- E3 ligase MDM2 mediates urea transporter-A1 ubiquitination under either constitutive or stimulatory conditions.American journal of physiology. Renal physiology · 2019Article
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A.Scientific reports · 2019Article
- Considering the Role of Murine Double Minute 2 in the Cardiovascular System?Frontiers in cell and developmental biology · 2019Review
- Repeated shock stress facilitates basolateral amygdala synaptic plasticity through decreased cAMP-specific phosphodiesterase type IV (PDE4) expression.Brain structure & function · 2018Article
- Modulation of Compartmentalised Cyclic Nucleotide Signalling via Local Inhibition of Phosphodiesterase Activity.International journal of molecular sciences · 2016Review
- RACK1 and β-arrestin2 attenuate dimerization of PDE4 cAMP phosphodiesterase PDE4D5.Cellular signalling · 2016Article
- Heat shock protein 20 (HSP20) is a novel substrate for protein kinase D1 (PKD1).Cell biochemistry and function · 2015Article
- Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains.Cellular signalling · 2015Article
- The activity of cAMP-phosphodiesterase 4D7 (PDE4D7) is regulated by protein kinase A-dependent phosphorylation within its unique N-terminus.FEBS letters · 2015Article
- Small heat shock protein 20 (Hsp20) facilitates nuclear import of protein kinase D 1 (PKD1) during cardiac hypertrophy.Cell communication and signaling : CCS · 2015Article
- The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence.Channels (Austin, Tex.) · 2015Review
- β-Arrestins 1 and 2 are critical regulators of inflammation.Innate immunity · 2014Review
- Heart failure-specific changes in protein kinase signalling.Pflugers Archiv : European journal of physiology · 2014Review
- Phosphorylation regulates TRPV1 association with β-arrestin-2.The Biochemical journal · 2013Article
- RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency.Cellular and molecular life sciences : CMLS · 2013Article
- β-Arrestin-2 desensitizes the transient receptor potential vanilloid 1 (TRPV1) channel.The Journal of biological chemistry · 2012Article
- Inhibition of phosphodiesterase-4 (PDE4) activity triggers luminal apoptosis and AKT dephosphorylation in a 3-D colonic-crypt model.Molecular cancer · 2012Article
- Deciphering enzyme function using peptide arrays.Molecular biotechnology · 2011Review
Corrections and comments
- Correction · 2009-08-01Error in Text · Updated to Retraction · · see also: https://pubpeer.com/publications/0B069B46C40C6442C30F0D0BACCD68
- Retraction · 2020-08-21Duplication of/in Image · Upgrade/Update of Prior Notice(s) · · see also: https://pubpeer.com/publications/0B069B46C40C6442C30F0D0BACCD68
- Erratum issued
- Retracted
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Beta-arrestin plays a key role in regulating beta2-adrenoreceptor signaling by interdicting activation of adenylyl cyclase and selectively sequestering cAMP phosphodiesterase-4D5 (PDE4D5) for delivery of an active cAMP degrading system to the site of cAMP synthesis. Here we show that the beta-agonist, isoprenaline, triggers the rapid and transient ubiquitination of PDE4D5 in primary cardiomyocytes, mouse embryo fibroblasts, and HEK293B2 cells constitutively expressing beta2-adrenoceptors. Reconstitution analyses in beta-arrestin1/2 double knockout cells plus small interference RNA knockdown studies indicate that a beta-arrestin-scaffolded pool of the E3-ubiquitin ligase, Mdm2, mediates PDE4D5 ubiquitination. Critical for this is the ubiquitin-interacting motif located in the extreme C terminus of PDE4D5, which is specific to the PDE4D sub-family. In vitro ubiquitination [corrected] of a PDE4D5 spot-immobilized peptide array, followed by a mutagenesis strategy, showed that PDE4D5 ubiquitination occurs at Lys-48, Lys-53, and Lys-78, which are located within its isoform-specific N-terminal region, as well as at Lys-140 located within its regulatory UCR1 module. We suggest that mono-ubiquitination at Lys-140 primes PDE4D5 for a subsequent cascade of polyubiquitination occurring within its isoform-specific N-terminal region at Lys-48, Lys-53, and Lys-78. PDE4D5 interacts with a non-ubiquitinated beta-arrestin sub-population that is likely to be protected from Mdm2-mediated ubiquitination due to steric hindrance caused by sequestered PDE4D5. Ubiquitination of PDE4D5 elicits an increase in the fraction of PDE4D5 sequestered by beta-arrestin in cells, thereby contributing to the fidelity of PDE4D5-beta-arrestin interaction, as well as decreasing the fraction of PDE4D5 sequestered by the scaffolding protein, RACK1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.