PDE4D

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PDE4D
Protein PDE4D PDB 1mkd.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases PDE4D, ACRDYS2, DPDE3, HSPDE43, PDE4DN2, STRK1, phosphodiesterase 4D
External IDs HomoloGene: 129755 GeneCards: PDE4D
Genetically Related Diseases
breast cancer, obesity, smallpox, esophageal cancer, asthma[1]
Targeted by Drug
rolipram[2]
RNA expression pattern
PBB GE PDE4D 210836 x at tn.png

PBB GE PDE4D 210837 s at tn.png

PBB GE PDE4D 211840 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC) Chr 5: 58.97 – 60.52 Mb n/a
PubMed search [3] n/a
Wikidata
View/Edit Human

cAMP-specific 3',5'-cyclic phosphodiesterase 4D is an enzyme that in humans is encoded by the PDE4D gene.

Function[edit]

The PDE4D gene is complex and has at least 9 different isoforms that encode functional proteins. These proteins degrade the second messenger cAMP, which is a key signal transduction molecule in multiple cell types, including vascular cells (Dominiczak and McBride, 2003).[supplied by OMIM][4]

Interactions[edit]

PDE4D has been shown to interact with myomegalin[5] and GNB2L1.[6][7]

Clinical relevance[edit]

Mutations in this gene have been associated to cases of acrodysostosis.[8]

This is the subtype of PDE4 that appears to be involved in the emetic and antidepressant effects of PDE4 inhibitors.[9]

Furthermore, changes in expression of the isoform PDE4D7 have been proposed as prostate cancer biomarker. [10] [11]

References[edit]

  1. ^ "Diseases that are genetically associated with PDE4D view/edit references on wikidata". 
  2. ^ "Drugs that physically interact with Phosphodiesterase 4D view/edit references on wikidata". 
  3. ^ "Human PubMed Reference:". 
  4. ^ "Entrez Gene: PDE4D phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)". 
  5. ^ Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M (Apr 2001). "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal of Biological Chemistry. 276 (14): 11189–98. doi:10.1074/jbc.M006546200. PMID 11134006. 
  6. ^ Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB (May 1999). "The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform". The Journal of Biological Chemistry. 274 (21): 14909–17. doi:10.1074/jbc.274.21.14909. PMID 10329691. 
  7. ^ Steele MR, McCahill A, Thompson DS, MacKenzie C, Isaacs NW, Houslay MD, Bolger GB (Jul 2001). "Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5". Cellular Signalling. 13 (7): 507–13. doi:10.1016/S0898-6568(01)00167-X. PMID 11516626. 
  8. ^ Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V (Apr 2012). "Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis". American Journal of Human Genetics. 90 (4): 740–5. doi:10.1016/j.ajhg.2012.03.003. PMID 22464250. 
  9. ^ Zhang HT (2009). "Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs". Current Pharmaceutical Design. 15 (14): 1688–98. doi:10.2174/138161209788168092. PMID 19442182. 
  10. ^ Böttcher R, Henderson DJ, Dulla K, van Strijp D, Waanders LF, Tevz G, Lehman ML, Merkle D, van Leenders GJ, Baillie GS, Jenster G, Houslay MD, Hoffmann R (Nov 2015). "Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG-positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression.". British Journal of Cancer. 113 (10): 1502–11. doi:10.1038/bjc.2015.335. PMID 26575822. 
  11. ^ Henderson DJ, Byrne A, Dulla K, Jenster G, Hoffmann R, Baillie GS, Houslay MD (Mar 2014). "The cAMP phosphodiesterase-4D7 (PDE4D7) is downregulated in androgen-independent prostate cancer cells and mediates proliferation by compartmentalising cAMP at the plasma membrane of VCaP prostate cancer cells.". British Journal of Cancer. 110 (5): 1278–87. doi:10.1038/bjc.2014.22. PMC 3950871Freely accessible. PMID 24518597. 

Further reading[edit]