ArticleMolecular and cellular biology2010
Evolutionarily conserved role of calcineurin in phosphodegron-dependent degradation of phosphodiesterase 4D.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
19 citing papers in PubMed, 31 citations in OpenAlex.
- Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.The FEBS journal · 2025Review
- Chemical, Biochemical, and Structural Similarities and Differences of Dermatological cAMP Phosphodiesterase-IV Inhibitors.The Journal of investigative dermatology · 2025Article
- Review
- Interrogating the Etiology of Sporadic Alzheimer's Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Role of the Glycogen Synthase Kinase 3-Cyclic AMP/Protein Kinase A in the Immobilization of Human Sperm by Tideglusib.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits.Frontiers in neuroanatomy · 2020Article
- 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
- Article
- Molecular inotropy mediated by cardiac miR-based PDE4D/PRKAR1α/phosphoprotein signaling.Scientific reports · 2016Article
- A dynamic interface between ubiquitylation and cAMP signaling.Frontiers in pharmacology · 2015Review
- Role of extracellular signal-regulated kinase 5 in adipocyte signaling.The Journal of biological chemistry · 2014Article
- Ablation of calcineurin Aβ reveals hyperlipidemia and signaling cross-talks with phosphodiesterases.The Journal of biological chemistry · 2013Article
- Article
- Acute calcineurin inhibition with tacrolimus increases phosphorylated UT-A1.American journal of physiology. Renal physiology · 2012Article
- DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness.ACS chemical neuroscience · 2011Article
- Co-ordinated action of DISC1, PDE4B and GSK3β in modulation of cAMP signalling.Molecular psychiatry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
Abstract
Calcineurin is a widely expressed and highly conserved Ser/Thr phosphatase. Calcineurin is inhibited by the immunosuppressant drug cyclosporine A (CsA) or tacrolimus (FK506). The critical role of CsA/FK506 as an immunosuppressant following transplantation surgery provides a strong incentive to understand the phosphatase calcineurin. Here we uncover a novel regulatory pathway for cyclic AMP (cAMP) signaling by the phosphatase calcineurin which is also evolutionarily conserved in Caenorhabditis elegans. We found that calcineurin binds directly to and inhibits the proteosomal degradation of cAMP-hydrolyzing phosphodiesterase 4D (PDE4D). We show that ubiquitin conjugation and proteosomal degradation of PDE4D are controlled by a cullin 1-containing E(3) ubiquitin ligase complex upon dual phosphorylation by casein kinase 1 (CK1) and glycogen synthase kinase 3beta (GSK3beta) in a phosphodegron motif. Our findings identify a novel signaling process governing G-protein-coupled cAMP signal transduction-opposing actions of the phosphatase calcineurin and the CK1/GSK3beta protein kinases on the phosphodegron-dependent degradation of PDE4D. This novel signaling system also provides unique functional insights into the complications elicited by CsA in transplant patients.
Indexed as
Identifiers
What OpenQuestion holds
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.