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Gene Review

PDE4B  -  phosphodiesterase 4B, cAMP-specific

Homo sapiens

Synonyms: DPDE4, PDE32, PDEIVB, cAMP-specific 3',5'-cyclic phosphodiesterase 4B
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Disease relevance of PDE4B


High impact information on PDE4B

  • LPS stimulation of mouse peripheral leukocytes induced PDE4B mRNA accumulation and increased PDE4 activity [5].
  • These findings demonstrate that PDE4B gene activation by LPS constitutes a feedback regulation essential for an efficient immune response [5].
  • Hence, DLBCLs that express high PDE4B levels may be resistant to cAMP-induced apoptosis, contributing to their less favorable outcome [2].
  • Herein, we confirmed the risk-related expression of PDE4B in an independent series of primary DLBCLs and defined the enzyme's role in modulating cAMP-induced apoptosis in parental DLBCL cell lines or those reconstituted with wild-type or mutant PDE4B [2].
  • Phosphodiesterase 4B (PDE4B) inactivates the second messenger cyclic adenosine 3',5' monophosphate (cAMP) and abrogates its inhibitory effects in B lymphocytes [2].

Biological context of PDE4B


Anatomical context of PDE4B

  • In CD4 and CD8 lymphocytes PDE4A, PDE4B and PDE4D were detected, with no significant differences observed between healthy and asthmatic groups [11].
  • 5. These results suggest that PDE4A and/or PDE4B may play the major role in regulating these two inflammatory cell functions but do not rule out PDE4D as an important mediator of other activities in mononuclear leukocytes and other immune and inflammatory cells [8].
  • DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype [12].
  • In peripheral blood T cells, two previously reported PDE4B isoforms could be detected: one was 75-80 kDa (PDE4B1) and the other was 65-67 kDa (PDE4B2) [9].
  • In the present study, we demonstrate, for the first time, that lipopolysaccharide (LPS) significantly and selectively stimulated PDE4B mRNA production in human monocytes [13].

Associations of PDE4B with chemical compounds


Regulatory relationships of PDE4B

  • In this study, we show that the PDE4B gene is constitutively expressed in neutrophils and that this expression remains unaffected by LPS or IL-10 [10].

Other interactions of PDE4B

  • Using semi-quantitative RT-PCR, we detected a 50-70% decrease in the mRNA of PDE4A and PDE4B subtypes following Dex treatment [16].
  • PDE4A and PDE4B mRNAs also are markedly abundant, whereas lower expression is observed for PDE4C mRNAs [17].
  • To identify amino acid residues involved in PDE3-selective inhibitor binding, we selected eight presumed interacting residues in the substrate-binding pocket of PDE3A using a model created on basis of homology to the PDE4B crystal structure [18].
  • A model of PDE3B was constructed based on the X-ray crystal structure of PDE4B [19].
  • All of the 4 expressed isoforms of PDE (PDE1C, PDE2, PDE 4A, and PDE4B) were increased in mRNA expression; the levels of PKA RIalpha, RIbeta, and RIIbeta were increased moderately, however, those of RIIalpha and Calpha were increased remarkably [20].

Analytical, diagnostic and therapeutic context of PDE4B


  1. A role for cyclic nucleotide phosphodiesterase 4 in regulation of the growth of human malignant melanoma cells. Narita, M., Murata, T., Shimizu, K., Nakagawa, T., Sugiyama, T., Inui, M., Hiramoto, K., Tagawa, T. Oncol. Rep. (2007) [Pubmed]
  2. The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma. Smith, P.G., Wang, F., Wilkinson, K.N., Savage, K.J., Klein, U., Neuberg, D.S., Bollag, G., Shipp, M.A., Aguiar, R.C. Blood (2005) [Pubmed]
  3. Nitric oxide induces phosphodiesterase 4B expression in rat pulmonary artery smooth muscle cells. Busch, C.J., Liu, H., Graveline, A.R., Bloch, K.D. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  4. Characterization of two human cAMP-specific phosphodiesterase subtypes expressed in baculovirus-infected insect cells. Amegadzie, B.Y., Hanning, C.R., McLaughlin, M.M., Burman, M., Cieslinski, L.B., Livi, G.P., Torphy, T.J. Cell Biol. Int. (1995) [Pubmed]
  5. Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Jin, S.L., Conti, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Saldou, N., Obernolte, R., Huber, A., Baecker, P.A., Wilhelm, R., Alvarez, R., Li, B., Xia, L., Callan, O., Su, C., Jarnagin, K., Shelton, E.R. Cell. Signal. (1998) [Pubmed]
  7. Prolonged beta adrenoceptor stimulation up-regulates cAMP phosphodiesterase activity in human monocytes by increasing mRNA and protein for phosphodiesterases 4A and 4B. Manning, C.D., McLaughlin, M.M., Livi, G.P., Cieslinski, L.B., Torphy, T.J., Barnette, M.S. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  8. Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B. Manning, C.D., Burman, M., Christensen, S.B., Cieslinski, L.B., Essayan, D.M., Grous, M., Torphy, T.J., Barnette, M.S. Br. J. Pharmacol. (1999) [Pubmed]
  9. Specific CD3 epsilon association of a phosphodiesterase 4B isoform determines its selective tyrosine phosphorylation after CD3 ligation. Baroja, M.L., Cieslinski, L.B., Torphy, T.J., Wange, R.L., Madrenas, J. J. Immunol. (1999) [Pubmed]
  10. Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils. Wang, P., Wu, P., Ohleth, K.M., Egan, R.W., Billah, M.M. Mol. Pharmacol. (1999) [Pubmed]
  11. Identification and quantification of phosphodiesterase 4 subtypes in CD4 and CD8 lymphocytes from healthy and asthmatic subjects. Landells, L.J., Szilagy, C.M., Jones, N.A., Banner, K.H., Allen, J.M., Doherty, A., O'Connor, B.J., Spina, D., Page, C.P. Br. J. Pharmacol. (2001) [Pubmed]
  12. DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype. Jacob, C., Leport, M., Szilagyi, C., Allen, J.M., Bertrand, C., Lagente, V. Int. Immunopharmacol. (2002) [Pubmed]
  13. Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes. Ma, D., Wu, P., Egan, R.W., Billah, M.M., Wang, P. Mol. Pharmacol. (1999) [Pubmed]
  14. Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia. Moon, E., Lee, R., Near, R., Weintraub, L., Wolda, S., Lerner, A. Clin. Cancer Res. (2002) [Pubmed]
  15. Cyclic AMP phosphodiesterases in the zebra finch: distribution, cloning and characterization of a PDE4B homolog. Thompson, B.E., Freking, F., Pho, V., Schlinger, B.A., Cherry, J.A. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  16. Dexamethasone down-regulates cAMP-phosphodiesterase in human osteosarcoma cells. Ahlström, M., Pekkinen, M., Huttunen, M., Lamberg-Allardt, C. Biochem. Pharmacol. (2005) [Pubmed]
  17. Effect of pregnancy on PDE4 cAMP-specific phosphodiesterase messenger ribonucleic acid expression in human myometrium. Leroy, M.J., Méhats, C., Duc-Goiran, P., Tanguy, G., Robert, B., Dallot, E., Mignot, T.M., Grangé, G., Ferré, F. Cell. Signal. (1999) [Pubmed]
  18. Identification of interaction sites of cyclic nucleotide phosphodiesterase type 3A with milrinone and cilostazol using molecular modeling and site-directed mutagenesis. Zhang, W., Ke, H., Colman, R.W. Mol. Pharmacol. (2002) [Pubmed]
  19. The role of tryptophan 1072 in human PDE3B inhibitor binding. Chung, C., Varnerin, J.P., Morin, N.R., MacNeil, D.J., Singh, S.B., Patel, S., Scapin, G., Van der Ploeg, L.H., Tota, M.R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  20. Adaptation of cAMP signaling system in SH-SY5Y neuroblastoma cells following expression of a constitutively active stimulatory G protein alpha, Q227L Gsalpha. Jang, I.S., Juhnn, Y.S. Exp. Mol. Med. (2001) [Pubmed]
  21. Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3. Huston, E., Lumb, S., Russell, A., Catterall, C., Ross, A.H., Steele, M.R., Bolger, G.B., Perry, M.J., Owens, R.J., Houslay, M.D. Biochem. J. (1997) [Pubmed]
  22. Identification of overlapping but distinct cAMP and cGMP interaction sites with cyclic nucleotide phosphodiesterase 3A by site-directed mutagenesis and molecular modeling based on crystalline PDE4B. Zhang, W., Ke, H., Tretiakova, A.P., Jameson, B., Colman, R.W. Protein Sci. (2001) [Pubmed]
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