ArticleThe Biochemical journal2006
Scanning peptide array analyses identify overlapping binding sites for the signalling scaffold proteins, beta-arrestin and RACK1, in cAMP-specific phosphodiesterase PDE4D5.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 147 citations in OpenAlex.
- Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.Expert opinion on therapeutic targets · 2024Review
- Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?Brain communications · 2024Review
- SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to CaThe FEBS journal · 2022Article
- Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.Journal of molecular and cellular cardiology · 2022Article
- Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The RanBP2/RanGAP1-SUMO complex gates β-arrestin2 nuclear entry to regulate the Mdm2-p53 signaling axis.Oncogene · 2021Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma.Molecular biology reports · 2020Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system.Molecular psychiatry · 2018Article
- PDE4-Mediated cAMP Signalling.Journal of cardiovascular development and disease · 2018Review
- Targeting phosphodiesterase 4 as a potential therapeutic strategy for enhancing neuroplasticity following ischemic stroke.International journal of biological sciences · 2018Review
- Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B action in hippocampus.BMC neuroscience · 2017Article
- The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1.Cellular signalling · 2017Article
- Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington's disease.The Journal of clinical investigation · 2017Article
- Identification of a multifunctional docking site on the catalytic unit of phosphodiesterase-4 (PDE4) that is utilised by multiple interaction partners.The Biochemical journal · 2017Article
- 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
- Distinct structural domains of caveolin-1 independently regulate Ca2+ release-activated Ca2+ channels and Ca2+ microdomain-dependent gene expression.Molecular and cellular biology · 2015Article
- Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains.Cellular signalling · 2015Article
1 more citing papers are in PubMed but not listed here.
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12 authors at 1 institution in 1 country.
Funding
Abstract
The cAMP-specific phosphodiesterase PDE4D5 can interact with the signalling scaffold proteins RACK (receptors for activated C-kinase) 1 and beta-arrestin. Two-hybrid and co-immunoprecipitation analyses showed that RACK1 and beta-arrestin interact with PDE4D5 in a mutually exclusive manner. Overlay studies with PDE4D5 scanning peptide array libraries showed that RACK1 and beta-arrestin interact at overlapping sites within the unique N-terminal region of PDE4D5 and at distinct sites within the conserved PDE4 catalytic domain. Screening scanning alanine substitution peptide arrays, coupled with mutagenesis and truncation studies, allowed definition of RACK1 and beta-arrestin interaction sites. Modelled on the PDE4D catalytic domain, these form distinct well-defined surface-exposed patches on helices-15-16, for RACK1, and helix-17 for beta-arrestin. siRNA (small interfering RNA)-mediated knockdown of RACK1 in HEK-293 (human embryonic kidney) B2 cells increased beta-arrestin-scaffolded PDE4D5 approx. 5-fold, increased PDE4D5 recruited to the beta2AR (beta2-adrenergic receptor) upon isoproterenol challenge approx. 4-fold and severely attenuated (approx. 4-5 fold) both isoproterenol-stimulated PKA (protein kinase A) phosphorylation of the beta2AR and activation of ERK (extracellular-signal-regulated kinase). The ability of a catalytically inactive form of PDE4D5 to exert a dominant negative effect in amplifying isoproterenol-stimulated ERK activation was ablated by a mutation that blocked the interaction of PDE4D5 with beta-arrestin. In the present study, we show that the signalling scaffold proteins RACK1 and beta-arrestin compete to sequester distinct 'pools' of PDE4D5. In this fashion, alterations in the level of RACK1 expression may act to modulate signal transduction mediated by the beta2AR.
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