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PDE4 Associates with Different Scaffolding Proteins: Modulating Interactions as Treatment for Certain Diseases

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Protein-Protein Interactions as New Drug Targets

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 186))

Abstract

cAMP is an ubiquitous second messenger that is crucial to many cellular processes. The sole means of terminating the cAMP signal is degradation by cAMP phosphodiesterases (PDEs). The PDE4 family is of particular interest because PDE4 inhibitors have therapeutic potential for the treatment of various inflammatory and auto-immune diseases and also have anti-depressant and memory-enhancing effects. The subcellular targeting of PDE4 isoforms is fundamental to the compartmentalization of cAMP signaling pathways and is largely achieved via proteinprotein interactions. Increased knowledge of these protein-protein interactions and their regulatory properties could aid in the design of novel isoform-specific inhibitors with improved efficacy and fewer prohibitive side effects.

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References

  • Adessi C, Soto C (2002) Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem 9:963–978

    Article  PubMed  CAS  Google Scholar 

  • Ariga M, Neitzert B, Nakae S, Mottin G, Bertrand C, Pruniaux MP, Jin SL, Conti M (2004) Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammation. J Immunol 173:7531–7538

    PubMed  CAS  Google Scholar 

  • Alvarez R, Sette C, Yang D, Eglen RM, Wilhelm R, Shelton ER, Conti M (1995) Activation and selective inhibition of camp specific phosphodiesterases, PDE4D3. Mol Pharmacol 48:616–622

    PubMed  CAS  Google Scholar 

  • Baillie GS, Houslay MD (2005) Arrestin times for compartmentalised cAMP signalling and phosphodiesterase-4 enzymes. Curr Opin Cell Biol 17:129–134

    Article  PubMed  CAS  Google Scholar 

  • Baillie GS, Mackenzie SJ, Houslay MD (2001) PMA triggers the PKA-mediated phosphorylation and activation of the PDE4D5 cAMP phosphodiesterase in human aortic smooth muscle cells through a route involving Extracellular Signal Regulated Kinase (ERK). Mol Pharmacol 60:1100–1111

    PubMed  CAS  Google Scholar 

  • Baillie GS, Huston E, Scotland G, Hodgkin M, Gall I, Peden AH, MacKenzie C, Houslay ES, Currie R, Pettitt TR, Walmsley AR, Wakelam MJ, Warwicker J, Houslay MD (2002) TAPAS-1, a novel microdomain within the unique N-terminal region of the PDE4A1 cAMP-specific phosphodiesterase that allows rapid, Ca2+-triggered membrane association with selectivity for interaction with phosphatidic acid. J Biol Chem 277:28298–28309

    Article  PubMed  CAS  Google Scholar 

  • Baillie GS, Sood A, McPhee I, Gall I, Perry SJ, Lefkowitz RJ, Houslay MD (2003) beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. Proc Natl Acad Sci USA 100:940–945

    Article  PubMed  CAS  Google Scholar 

  • Baillie GS, Scott JD, Houslay MD (2005) Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract. FEBS Lett 579:3264–3270

    Article  PubMed  CAS  Google Scholar 

  • Baillie GS, Adams DR, Bahri N, Houslay TM, Vadrevu S, Meng D, Li X, Dunlop A, Milligan G, Bolger GB, Klussmann E, Houslay MD (2007) Mapping binding sites for the PDE4D5 cAMP-specific phosphodiesterase to the N- and C-domains of betaarrestin using spot-immobilised peptide arrays. Biochem J 404:71–80

    Article  PubMed  CAS  Google Scholar 

  • Barnette MS (1999) Phosphodiesterase 4 (PDE4) inhibitors in asthma and chronic obstructive pulmonary disease (COPD). Prog Drug Res 53:193–229

    PubMed  CAS  Google Scholar 

  • Barnette MS, Underwood DC (2000) New phosphodiesterase inhibitors as therapeutics for the treatment of chronic lung disease. Curr Opin Pulm Med 6:164–169

    Article  PubMed  CAS  Google Scholar 

  • Beard MB, O’Connell JC, Bolger GB, Houslay MD (1999) The unique N-terminal domain of the cAMP phosphodiesterase PDE4D4 allows for interaction with specific SH3 domains. FEBS Lett 460:173–177

    Article  PubMed  CAS  Google Scholar 

  • Beard MB, Olsen AE, Jones RE, Erdogan S, Houslay MD, Bolger GB (2000) UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions. J Biol Chem 275:10349–10358

    Article  PubMed  CAS  Google Scholar 

  • Beard MB, Huston E, Campbell L, Gall I, McPhee I, Yarwood S, Scotland G, Houslay MD (2002) In addition to the SH3 binding region, multiple regions within the N-terminal noncatalytic portion of the cAMP-specific phosphodiesterase, PDE4A5, contribute to its intracellular targeting. Cell Signal 14:453–465

    Article  PubMed  CAS  Google Scholar 

  • Beavo JA, Brunton LL (2002) Cyclic nucleotide research – still expanding after half a century. Nat Rev Mol Cell Biol 3:710–718

    Article  PubMed  CAS  Google Scholar 

  • Bock KW, Kohle C (2006) Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem Pharmacol 72:393–404

    Article  PubMed  CAS  Google Scholar 

  • Bolger GB (1994) Molecular biology of the cyclic AMP-specific cyclic nucleotide phosphodiesterases: a diverse family of regulatory enzymes. Cell Signal 6:851–859

    Article  PubMed  CAS  Google Scholar 

  • Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K (1993) A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. Mol Cell Biol 13:6558–6571

    PubMed  CAS  Google Scholar 

  • Bolger GB, Erdogan S, Jones RE, Loughney K, Scotland G, Hoffmann R, Wilkinson I, Farrell C, Houslay MD (1997) Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene. Biochem J 328(Pt 2):539–548

    PubMed  CAS  Google Scholar 

  • Bolger GB, McCahill A, Yarwood SJ, Steele MR, Warwicker J, Houslay MD (2002) Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5. BMC Biochem 3:24

    Article  PubMed  Google Scholar 

  • Bolger GB, McCahill A, Huston E, Cheung YF, McSorley T, Baillie GS, Houslay MD (2003a) The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with beta-arrestins. J Biol Chem 278:49230–49238

    Article  PubMed  CAS  Google Scholar 

  • Bolger GB, Peden AH, Steele MR, MacKenzie C, McEwan DG, Wallace DA, Huston E, Baillie GS, Houslay MD (2003b) Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2. J Biol Chem 278:33351–33363

    Article  PubMed  CAS  Google Scholar 

  • Bolger GB, Baillie GS, Li X, Lynch MJ, Herzyk P, Mohamed A, Mitchell LH, McCahill A, Hundsrucker C, Klussmann E, Adams DR, Houslay MD (2006) Scanning peptide array analyses identify overlapping binding sites for the signalling scaffold proteins, beta-arrestin and RACK1, in cAMP-specific phosphodiesterase PDE4D5. Biochem J 398:23–36

    Article  PubMed  CAS  Google Scholar 

  • Bolger G, Conti M, Houslay MD (2007) Cellular functions of PDE4 enzymes. In: Beavo JA, Francis SH, Houslay MD (eds) Cyclic nucleotide phosphodiesterases in health and disease. CRC Press, Boca Raton, London, New York, pp 99–130

    Google Scholar 

  • Bos JL (2003) Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4:733–738

    Article  PubMed  CAS  Google Scholar 

  • Bos JL (2006) Epac proteins: multi-purpose cAMP targets. Trends Biochem Sci 31:680–686.

    Article  PubMed  CAS  Google Scholar 

  • Boswell-Smith V, Spina D, Page CP (2006) Phosphodiesterase inhibitors. Br J Pharmacol 147 (Suppl 1):S252–S257

    Article  PubMed  CAS  Google Scholar 

  • Brunton LL (2003) PDE4: arrested at the border. Sci STKE 2003:PE44

    Article  PubMed  Google Scholar 

  • Brunton LL, Hayes JS, Mayer SE (1981) Functional compartmentation of cyclic AMP and protein kinase in heart. Adv Cyclic Nucleotide Res 14:391–397

    PubMed  CAS  Google Scholar 

  • Burnouf C, Pruniaux MP (2002) Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs. Curr Pharm Des 8:1255–1296

    Article  PubMed  CAS  Google Scholar 

  • Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY (2004) Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure 12:2233–2247

    Article  PubMed  CAS  Google Scholar 

  • Carlisle Michel JJ, Dodge KL, Wong W, Mayer NC, Langeberg LK, Scott JD (2004) PKA-phosphorylation of PDE4D3 facilitates recruitment of the mAKAP signalling complex. Biochem J 381:587–592

    Article  PubMed  CAS  Google Scholar 

  • Carson CC, Lue TF (2005) Phosphodiesterase type 5 inhibitors for erectile dysfunction. BJU Int 96:257–280

    Article  PubMed  CAS  Google Scholar 

  • Carter CJ (2006) Schizophrenia susceptibility genes converge on interlinked pathways related to glutamatergic transmission and long-term potentiation, oxidative stress and oligodendrocyte viability. Schizophr Res 86:1–14

    Article  PubMed  CAS  Google Scholar 

  • Carver LA, Bradfield CA (1997) Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. J Biol Chem 272:11452–11456

    Article  PubMed  CAS  Google Scholar 

  • Chang BY, Chiang M, Cartwright CA (2001) The interaction of Src and RACK1 is enhanced by activation of protein kinase C and tyrosine phosphorylation of RACK1. J Biol Chem 276:20346–20356

    Article  PubMed  CAS  Google Scholar 

  • Colledge M, Scott JD (1999) AKAPs: from structure to function. Trends Cell Biol 9:216–221

    Article  PubMed  CAS  Google Scholar 

  • Conti M (2002) Specificity of the cyclic adenosine 3′,5′-monophosphate signal in granulosa cell function. Biol Reprod 67:1653–1661

    Article  PubMed  CAS  Google Scholar 

  • Conti M, Jin SL (1999) The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 63:1–38

    Article  PubMed  CAS  Google Scholar 

  • Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481–511

    Article  PubMed  CAS  Google Scholar 

  • Conti M, Richter W, Mehats C, Livera G, Park JY, Jin C (2003) Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling. J Biol Chem 278:5493–5496

    Article  PubMed  CAS  Google Scholar 

  • Cooper DM (2003) Regulation and organization of adenylyl cyclases and cAMP. Biochem J 375:517–529

    Article  PubMed  CAS  Google Scholar 

  • Cooper DM (2005) Compartmentalization of adenylate cyclase and cAMP signalling. Biochem Soc Trans 33:1319–1322

    Article  PubMed  CAS  Google Scholar 

  • Cooper DM, Crossthwaite AJ (2006) Higher-order organization and regulation of adenylyl cyclases. Trends Pharmacol Sci 27:426–431

    Article  PubMed  CAS  Google Scholar 

  • Cowan-Jacob SW (2006) Structural biology of protein tyrosine kinases. Cell Mol Life Sci 63:2608–2625

    Article  PubMed  CAS  Google Scholar 

  • Daaka Y, Luttrell LM, Lefkowitz RJ (1997) Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature 390:88–91

    Article  PubMed  CAS  Google Scholar 

  • Davis RL, Cherry J, Dauwalder B, Han PL, Skoulakis E (1995) The cyclic AMP system and Drosophila learning. Mol Cell Biochem 149–150:271–278

    Article  PubMed  Google Scholar 

  • de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477

    Article  PubMed  CAS  Google Scholar 

  • DiPilato LM, Cheng X, Zhang J (2004) Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc Natl Acad Sci USA 101:16513–16518

    Article  PubMed  CAS  Google Scholar 

  • Diviani D, Baisamy L, Appert-Collin A (2006) AKAP-Lbc: a molecular scaffold for the integration of cyclic AMP and Rho transduction pathways. Eur J Cell Biol 85:603–610

    Article  PubMed  CAS  Google Scholar 

  • Dodge KL, Khouangsathiene S, Kapiloff MS, Mouton R, Hill EV, Houslay MD, Langeberg LK, Scott JD (2001) mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J 20:1921–1930

    Article  PubMed  CAS  Google Scholar 

  • Dodge-Kafka KL, Soughayer J, Pare GC, Carlisle Michel JJ, Langeberg LK, Kapiloff MS, Scott JD (2005) The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature 437:574–578

    Article  PubMed  CAS  Google Scholar 

  • Dolwick KM, Schmidt JV, Carver LA, Swanson HI, Bradfield CA (1993) Cloning and expression of a human Ah receptor cDNA. Mol Pharmacol 44:911–917

    PubMed  CAS  Google Scholar 

  • D’Sa C, Tolbert LM, Conti M, Duman RS (2002) Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice variants by cAMP signaling in primary cortical neurons. J Neurochem 81:745–757

    Article  PubMed  Google Scholar 

  • Dumaz N, Marais R (2005) Integrating signals between cAMP and the RAS/RAF/MEK/ERK signalling pathways. Based on the anniversary prize of the Gesellschaft fur Biochemie und Molekularbiologie Lecture delivered on 5 July 2003 at the Special FEBS Meeting in Brussels. FEBS J 272:3491–3504

    Article  PubMed  CAS  Google Scholar 

  • Fan Chung K (2006) Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol 533:110–117

    Article  PubMed  CAS  Google Scholar 

  • Fernandes-Alnemri T, Litwack G, Alnemri ES (1994) CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem 269:30761–30764

    PubMed  CAS  Google Scholar 

  • Frank R (2002) High-density synthetic peptide microarrays: emerging tools for functional genomics and proteomics. Comb Chem High Throughput Screen 5:429–440

    PubMed  CAS  Google Scholar 

  • Gao Y, Nikulina E, Mellado W, Filbin MT (2003) Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci 23:11770–11777

    PubMed  CAS  Google Scholar 

  • Ghavami A, Hirst WD, Novak TJ (2006) Selective phosphodiesterase (PDE)-4 inhibitors: a novel approach to treating memory deficit? Drugs R D 7:63–71

    Article  PubMed  CAS  Google Scholar 

  • Giembycz MA (2000) Phosphodiesterase 4 inhibitors and the treatment of asthma: where are we now and where do we go from here? Drugs 59:193–212

    Article  PubMed  CAS  Google Scholar 

  • Giembycz MA (2001) Cilomilast: a second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs 10:1361–1379

    Article  PubMed  CAS  Google Scholar 

  • Gretarsdottir S, Thorleifsson G, Reynisdottir ST, Manolescu A, Jonsdottir S, Jonsdottir T, Gudmundsdottir T, Bjarnadottir SM, Einarsson OB, Gudjonsdottir HM, Hawkins M, Gudmundsson G, Gudmundsdottir H, Andrason H, Gudmundsdottir AS, Sigurdardottir M, Chou TT, Nahmias J, Goss S, Sveinbjornsdottir S, Valdimarsson EM, Jakobsson F, Agnarsson U, Gudnason V, Thorgeirsson G, Fingerle J, Gurney M, Gudbjartsson D, Frigge ML, Kong A, Stefansson K, Gulcher JR (2003) The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet 35:131–138

    Article  PubMed  Google Scholar 

  • Hall RA (2004) Beta-adrenergic receptors and their interacting proteins. Semin Cell Dev Biol 15:281–288

    Article  PubMed  CAS  Google Scholar 

  • Hayes JS, Brunton LL (1982) Functional compartments in cyclic nucleotide action. J Cyclic Nucleotide Res 8:1–16

    PubMed  CAS  Google Scholar 

  • Hennah W, Thomson P, Peltonen L, Porteous D (2006) Genes and schizophrenia: beyond schizophrenia: the role of DISC1 in major mental illness. Schizophr Bull 32:409–416

    Article  PubMed  Google Scholar 

  • Hermanto U, Zong CS, Li W, Wang LH (2002) RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol 22:2345–2365

    Article  PubMed  CAS  Google Scholar 

  • Higashida H, Hoshi N, Zhang JS, Yokoyama S, Hashii M, Jin D, Noda M, Robbins J (2005) Protein kinase C bound with A-kinase anchoring protein is involved in muscarinic receptor-activated modulation of M-type KCNQ potassium channels. Neurosci Res 51:231–234

    Article  PubMed  CAS  Google Scholar 

  • Hill SJ (2006) G-protein-coupled receptors: past, present and future. Br J Pharmacol 147 (Suppl 1): S27–S37

    Article  PubMed  CAS  Google Scholar 

  • Hill EV, Sheppard CL, Cheung YF, Gall I, Krause E, Houslay MD (2006) Oxidative stress employs phosphatidyl inositol 3-kinase and ERK signalling pathways to activate cAMP phosphodiesterase-4D3 (PDE4D3) through multi-site phosphorylation at Ser239 and Ser579. Cell Signal 18:2056–2069

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann R, Wilkinson IR, McCallum JF, Engels P, Houslay MD (1998) cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and changes in rolipram inhibition triggered by protein kinase A phosphorylation of Ser-54: generation of a molecular model. Biochem J 333(Pt 1):139–149

    PubMed  CAS  Google Scholar 

  • Hoffmann R, Baillie GS, MacKenzie SJ, Yarwood SJ, Houslay MD (1999) The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. EMBO J 18:893–903

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD (1998) Adaptation in cyclic AMP signalling processes: a central role for cyclic AMP phosphodiesterases. Semin Cell Dev Biol 9:161–167

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD (2001) PDE4 cAMP-specific phosphodiesterases. Prog Nucleic Acid Res Mol Biol 69:249–315

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD (2005) The long and short of vascular smooth muscle phosphodiesterase-4 as a putative therapeutic target. Mol Pharmacol 68:563–567

    PubMed  CAS  Google Scholar 

  • Houslay MD (2006) A RSK(y) relationship with promiscuous PKA. Sci STKE 2006:pe32

    Article  PubMed  Google Scholar 

  • Houslay MD, Adams DR (2003) PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. Biochem J 370:1–18

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD, Kolch W (2000) Cell-type specific integration of cross-talk between extracellular signal-regulated kinase and cAMP signaling. Mol Pharmacol 58:659–668

    PubMed  CAS  Google Scholar 

  • Houslay MD, Milligan G (1997) Tailoring cAMP-signalling responses through isoform multiplicity. Trends Biochem Sci 22:217–224

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD, Sullivan M, Bolger GB (1998) The multienzyme PDE4 cyclic adenosine monophosphate-specific phosphodiesterase family: intracellular targeting, regulation, and selective inhibition by compounds exerting anti-inflammatory and antidepressant actions. Adv Pharmacol 44:225–342

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD, Schafer P, Zhang KY (2005) Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 10:1503–1519

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD, Baillie GS, Maurice, DH (2007) cAMP specific phosphodiesterase-4 enzymes in the cardiovascular system: a molecular toolbox for generating compartmentalised cAMP signalling. Circ Res 100:950–966

    Article  PubMed  CAS  Google Scholar 

  • Huang Z, Ducharme Y, Macdonald D, Robichaud A (2001) The next generation of PDE4 inhibitors. Curr Opin Chem Biol 5:432–438

    Article  PubMed  CAS  Google Scholar 

  • Huston E, Beard M, McCallum F, Pyne NJ, Vandenabeele P, Scotland G, Houslay MD (2000) The cAMP-specific phosphodiesterase PDE4A5 is cleaved downstream of its SH3 interaction domain by caspase-3. Consequences for altered intracellular distribution. J Biol Chem 275:28063–28074

    PubMed  CAS  Google Scholar 

  • Huston E, Pooley L, Julien P, Scotland G, McPhee I, Sullivan M, Bolger G, Houslay MD (1996) The human cyclic AMP-specific phosphodiesterase PDE-46 (HSPDE4A4B) expressed in transfected COS7 cells occurs as both particulate and cytosolic species that exhibit distinct kinetics of inhibition by the antidepressant rolipram. J Biol Chem 271:31334–31344

    Article  PubMed  CAS  Google Scholar 

  • Huston E, Gall I, Houslay TM, Houslay MD (2006a) Helix-1 of the cAMP-specific phosphodiesterase PDE4A1 regulates its phospholipase-D-dependent redistribution in response to release of Ca2+. J Cell Sci 119:3799–3810

    Article  PubMed  CAS  Google Scholar 

  • Huston E, Houslay TM, Baillie GS, Houslay MD (2006b) cAMP phosphodiesterase-4A1 (PDE4A1) has provided the paradigm for the intracellular targeting of phosphodiesterases, a process that underpins compartmentalized cAMP signalling. Biochem Soc Trans 34:504–509

    Article  PubMed  CAS  Google Scholar 

  • Jin SL, Swinnen JV, Conti M (1992) Characterization of the structure of a low Km, rolipram-sensitive cAMP phosphodiesterase. Mapping of the catalytic domain. J Biol Chem 267:18929–18939

    PubMed  CAS  Google Scholar 

  • Jin S, Lan L, Zoudilova M, Conti M (2005) Specific role of phosphodiesterase 4B in lipopolysaccharide-induced signaling in mouse macrophages. J Immunol 175:1523–1531

    PubMed  CAS  Google Scholar 

  • Jin C, Richter W, Conti M (2007) Insights into the physiological functions of PDE4 from knockout mice. In: Beavo JA, Francis SH, Houslay MD (eds) Cyclic nucleotide phosphodiesterases in health and disease. CRC Press, Boca Raton, London, New York, pp 323–346

    Google Scholar 

  • Johnson JA, Gray MO, Chen CH, Mochly-Rosen D (1996) A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J Biol Chem 271:24962–24966

    Article  PubMed  CAS  Google Scholar 

  • Johnston LA, Erdogan S, Cheung YF, Sullivan M, Barber R, Lynch MJ, Baillie GS, Van Heeke G, Adams DR, Huston E, Houslay MD (2004) Expression, intracellular distribution and basis for lack of catalytic activity of the PDE4A7 isoform encoded by the human PDE4A cAMP-specific phosphodiesterase gene. Biochem J 380:371–384

    Article  PubMed  CAS  Google Scholar 

  • Kapiloff MS, Schillace RV, Westphal AM, Scott JD (1999) mAKAP: an A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes. J Cell Sci 112(Pt 16): 2725–2736

    PubMed  CAS  Google Scholar 

  • Karpen JW, Rich TC (2001) The fourth dimension in cellular signaling. Science 293:2204–2205

    Article  PubMed  CAS  Google Scholar 

  • Ke H, Wang H (2007) Crystal structures of phosphodiesterases and implications on substrate specificity and inhibitor selectivity. Curr Top Med Chem 7:391–403

    Article  PubMed  CAS  Google Scholar 

  • Kiely PA, Leahy M, O’Gorman D, O’Connor R (2005) RACK1-mediated integration of adhesion and insulin-like growth factor I (IGF-I) signaling and cell migration are defective in cells expressing an IGF-I receptor mutated at tyrosines 1250 and 1251. J Biol Chem 280:7624–7633

    Article  PubMed  CAS  Google Scholar 

  • Kim DH, Lerner A (1998) Type 4 cyclic adenosine monophosphate phosphodiesterase as a therapeutic target in chronic lymphocytic leukemia. Blood 92:2484–2494

    PubMed  CAS  Google Scholar 

  • King LS, Kozono D, Agre P (2004) From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5:687–698

    Article  PubMed  CAS  Google Scholar 

  • Klauck TM, Faux MC, Labudda K, Langeberg LK, Jaken S, Scott JD (1996) Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein. Science 271:1589–1592

    Article  PubMed  CAS  Google Scholar 

  • Klussmann E, Maric K, Wiesner B, Beyermann M, Rosenthal W (1999) Protein kinase A anchoring proteins are required for vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells. J Biol Chem 274:4934–4938

    Article  PubMed  CAS  Google Scholar 

  • Kooistra MR, Corada M, Dejana E, Bos JL (2005) Epac1 regulates integrity of endothelial cell junctions through VE-cadherin. FEBS Lett 579:4966–4972

    Article  PubMed  CAS  Google Scholar 

  • Kuzhandaivelu N, Cong YS, Inouye C, Yang WM, Seto E (1996) XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation. Nucleic Acids Res 24:4741–4750

    Article  PubMed  CAS  Google Scholar 

  • Lees MJ, Peet DJ, Whitelaw ML (2003) Defining the role for XAP2 in stabilization of the dioxin receptor. J Biol Chem 278:35878–35888

    Article  PubMed  CAS  Google Scholar 

  • Le Jeune IR, Shepherd M, Van Heeke G, Houslay MD, Hall IP (2002) Cyclic AMP-dependent transcriptional up-regulation of phosphodiesterase 4D5 in human airway smooth muscle cells. Identification and characterization of a novel PDE4D5 promoter. J Biol Chem 277:35980–35989

    Article  PubMed  CAS  Google Scholar 

  • Lerner A, Epstein PM (2006) Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies. Biochem J 393:21–41

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Asuri S, Rebhun JF, Castro AF, Paranavitana NC, Quilliam LA (2006) The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane. J Biol Chem 281:2506–2514

    Article  PubMed  CAS  Google Scholar 

  • Liliental J, Chang DD (1998) Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit. J Biol Chem 273:2379–2383

    Article  PubMed  CAS  Google Scholar 

  • Lim J, Pahlke G, Conti M (1999) Activation of the cAMP-specific phosphodiesterase PDE4D3 by phosphorylation. Identification and function of an inhibitory domain. J Biol Chem 274:19677–19685

    Article  PubMed  CAS  Google Scholar 

  • Lipworth BJ (2005) Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet 365:167–175

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Palmer D, Jimmo SL, Tilley DG, Dunkerley HA, Pang SC, Maurice DH (2000) Expression of phosphodiesterase 4D (PDE4D) is regulated by both the cyclic AMP-dependent protein kinase and mitogen-activated protein kinase signaling pathways. A potential mechanism allowing for the coordinated regulation of PDE4D activity and expression in cells. J Biol Chem 275:26615–26624

    Article  PubMed  CAS  Google Scholar 

  • Lomo J, Blomhoff HK, Beiske K, Stokke T, Smeland EB (1995) TGF-beta 1 and cyclic AMP promote apoptosis in resting human B lymphocytes. J Immunol 154: 1634–1643

    PubMed  CAS  Google Scholar 

  • Lugnier C (2006) Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol Ther 109:366–398

    Article  PubMed  CAS  Google Scholar 

  • Luttrell LM, Lefkowitz RJ (2002) The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115:455–465

    PubMed  CAS  Google Scholar 

  • Lynch MJ, Baillie GS, Mohamed A, Li X, Maisonneuve C, Klussmann E, van Heeke G, Houslay MD (2005) RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells. J Biol Chem 280:33178–33189

    Article  PubMed  CAS  Google Scholar 

  • Ma Q, Whitlock JP Jr (1997) A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem 272:8878–8884

    Article  PubMed  CAS  Google Scholar 

  • Ma D, Wu P, Egan RW, Billah MM, Wang P (1999) Phosphodiesterase 4B gene transcription is activated by lipopolysaccharide and inhibited by interleukin-10 in human monocytes. Mol Pharmacol 55:50–57

    PubMed  CAS  Google Scholar 

  • MacKenzie SJ, Baillie GS, McPhee I, Bolger GB, Houslay MD (2000) ERK2 mitogen-activated protein kinase binding, phosphorylation, and regulation of the PDE4D cAMP-specific phosphodiesterases. The involvement of COOH-terminal docking sites and NH2-terminal UCR regions. J Biol Chem 275:16609–16617

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie SJ, Baillie GS, McPhee I, MacKenzie C, Seamons R, McSorley T, Millen J, Beard MB, van Heeke G, Houslay MD (2002) Long PDE4 cAMP specific phosphodiesterases are activated by protein kinase A-mediated phosphorylation of a single serine residue in Upstream Conserved Region 1 (UCR1). Br J Pharmacol 136:421–433

    Article  PubMed  CAS  Google Scholar 

  • Malbon CC, Tao J, Wang HY (2004) AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes. Biochem J 379:1–9

    Article  PubMed  CAS  Google Scholar 

  • Marchmont RJ, Houslay MD (1980) Insulin trigger, cyclic AMP-dependent activation and phosphorylation of a plasma membrane cyclic AMP phosphodiesterase. Nature 286:904–906

    Article  PubMed  CAS  Google Scholar 

  • Martinez JM, Afshari CA, Bushel PR, Masuda A, Takahashi T, Walker NJ (2002) Differential toxicogenomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in malignant and nonmalignant human airway epithelial cells. Toxicol Sci 69:409–423

    Article  PubMed  CAS  Google Scholar 

  • Martey CA, Baglole CJ, Gasiewicz TA, Sime PJ, Phipps RP (2005) The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 289:L391–L399

    Article  PubMed  CAS  Google Scholar 

  • Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2:599–609

    Article  PubMed  CAS  Google Scholar 

  • McCahill A, Warwicker J, Bolger GB, Houslay MD, Yarwood SJ (2002) The RACK1 scaffold protein: a dynamic cog in cell response mechanisms. Mol Pharmacol 62:1261–1273

    Article  PubMed  CAS  Google Scholar 

  • McCahill A, McSorley T, Huston E, Hill EV, Lynch MJ, Gall I, Keryer G, Lygren B, Tasken K, van Heeke G, Houslay MD (2005) In resting COS1 cells a dominant negative approach shows that specific, anchored PDE4 cAMP phosphodiesterase isoforms gate the activation, by basal cyclic AMP production, of AKAP-tethered protein kinase A type II located in the centrosomal region. Cell Signal 17:1158–1173

    Article  PubMed  CAS  Google Scholar 

  • McConkey DJ, Orrenius S, Jondal M (1990) Agents that elevate cAMP stimulate DNA fragmentation in thymocytes. J Immunol 145:1227–1230

    PubMed  CAS  Google Scholar 

  • McPhee I, Yarwood SJ, Scotland G, Huston E, Beard MB, Ross AH, Houslay ES, Houslay MD (1999) Association with the SRC family tyrosyl kinase LYN triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B. Consequences for rolipram inhibition. J Biol Chem 274:11796–11810

    Article  PubMed  CAS  Google Scholar 

  • Meschia JF, Brott TG, Brown RD Jr, Crook R, Worrall BB, Kissela B, Brown WM, Rich SS, Case LD, Evans EW, Hague S, Singleton A, Hardy J (2005) Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke. Ann Neurol 58:351–361

    Article  PubMed  CAS  Google Scholar 

  • Meyer BK, Petrulis JR, Perdew GH (2000) Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2. Cell Stress Chaperones 5:243–254

    Article  PubMed  CAS  Google Scholar 

  • Millar JK, Christie S, Porteous DJ (2003) Yeast two-hybrid screens implicate DISC1 in brain development and function. Biochem Biophys Res Commun 311:1019–1025

    Article  PubMed  CAS  Google Scholar 

  • Millar JK, Pickard BS, Mackie S, James R, Christie S, Buchanan SR, Malloy MP, Chubb JE, Huston E, Baillie GS, Thomson PA, Hill EV, Brandon NJ, Rain JC, Camargo LM, Whiting PJ, Houslay MD, Blackwood DH, Muir WJ, Porteous DJ (2005) DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 310:1187–1191

    Article  PubMed  CAS  Google Scholar 

  • Monaco L, Vicini E, Conti M (1994) Structure of two rat genes coding for closely related rolipram-sensitive cAMP phosphodiesterases. Multiple mRNA variants originate from alternative splicing and multiple start sites. J Biol Chem 269:347–357

    PubMed  CAS  Google Scholar 

  • Morales JL, Perdew GH (2007) Carboxyl terminus of hsc70-interacting protein (CHIP) can remodel mature aryl hydrocarbon teceptor (AhR) complexes and mediate ubiquitination of both the AhR and the 90 kDa heat-shock protein (hsp90) in vitro. Biochemistry 46:610–621

    Article  PubMed  CAS  Google Scholar 

  • Murdoch H, Mackie S, Collins DM, Hill EV, Bolger GG, Klussmann E, Porteous DJ, Millar JK, Houslay MD (2007) Isoform selective susceptibility of DISC1/phosphodiesterase-4 (PDE4) complexes to dissociation by elevated intracellular cAMP levels. J Neurosci 27:9513–9524

    Article  PubMed  CAS  Google Scholar 

  • Nagata S (1997) Apoptosis by death factor. Cell 88:355–365

    Article  PubMed  CAS  Google Scholar 

  • Nemoz G, Sette C, Conti M (1997) Selective activation of rolipram-sensitive, cAMP-specific phosphodiesterase isoforms by phosphatidic acid. Mol Pharmacol 51:242–249

    PubMed  CAS  Google Scholar 

  • Nikolaev VO, Bunemann M, Hein L, Hannawacker A, Lohse MJ (2004) Novel single chain cAMP sensors for receptor-induced signal propagation. J Biol Chem 279:37215–37218

    Article  PubMed  CAS  Google Scholar 

  • O’Connell JC, McCallum JF, McPhee I, Wakefield J, Houslay ES, Wishart W, Bolger G, Frame M, Houslay MD (1996) The SH3 domain of Src tyrosyl protein kinase interacts with the N-terminal splice region of the PDE4A cAMP-specific phosphodiesterase RPDE-6 (RNPDE4A5). Biochem J 318(Pt 1):255–261

    PubMed  Google Scholar 

  • O’Donnell JM, Zhang HT (2004) Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4). Trends Pharmacol Sci 25:158–163

    Article  PubMed  CAS  Google Scholar 

  • Oesch-Bartlomowicz B, Oesch F (1990) Phosphorylation of cytochrome P450 isoenzymes in intact hepatocytes and its importance for their function in metabolic processes. Arch Toxicol 64: 257–261

    Article  PubMed  CAS  Google Scholar 

  • Olsen AE, Bolger GB (2000) Physical mapping and promoter structure of the murine cAMP-specific phosphodiesterase pde4a gene. Mamm Genome 11:41–45

    Article  PubMed  CAS  Google Scholar 

  • Parkes JD, Thompson C, Brennan L, Gajraj N, Howcroft B, Ruiz J (1984) Rolipram in Parkinson’s disease. Adv Neurol 40:563–565

    PubMed  CAS  Google Scholar 

  • Pawson T, Gish GD (1992) SH2 and SH3 domains: from structure to function. Cell 71:359–362

    Article  PubMed  CAS  Google Scholar 

  • Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, Filbin MT, Bunge MB (2004) cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med 10:610–616

    Article  PubMed  CAS  Google Scholar 

  • Perry SJ, Baillie GS, Kohout TA, McPhee I, Magiera MM, Ang KL, Miller WE, McLean AJ, Conti M, Houslay MD, Lefkowitz RJ (2002) Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science 298:834–836

    Article  PubMed  CAS  Google Scholar 

  • Petrulis JR, Perdew GH (2002) The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem Biol Interact 141:25–40

    Article  PubMed  CAS  Google Scholar 

  • Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3:639–650

    Article  PubMed  CAS  Google Scholar 

  • Pooley L, Shakur Y, Rena G, Houslay MD (1997) Intracellular localization of the PDE4A cAMP-specific phosphodiesterase splice variant RD1 (RNPDE4A1A) in stably transfected human thyroid carcinoma FTC cell lines. Biochem J 321(Pt 1):177–185

    PubMed  CAS  Google Scholar 

  • Porteous DJ, Millar JK (2006) Disrupted in schizophrenia 1: building brains and memories. Trends Mol Med 12:255–261

    Article  PubMed  CAS  Google Scholar 

  • Ravipati G, McClung JA, Aronow WS, Peterson SJ, Frishman WH (2007) Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease. Cardiol Rev 15:76–86

    Article  PubMed  Google Scholar 

  • Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD (2001) Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10. Mol Pharmacol 59:996–1011

    PubMed  CAS  Google Scholar 

  • Richter W, Conti M (2002) Dimerization of the type 4 cAMP-specific phosphodiesterases is mediated by the upstream conserved regions (UCRs). J Biol Chem 277:40212–40221

    Article  PubMed  CAS  Google Scholar 

  • Richter W, Conti M (2004) The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterases. J Biol Chem 279:30338–30348

    Article  PubMed  CAS  Google Scholar 

  • Robichaud A, Tattersall FD, Choudhury I, Rodger IW (1999) Emesis induced by inhibitors of type IV cyclic nucleotide phosphodiesterase (PDE IV) in the ferret. Neuropharmacology 38:289–297

    Article  PubMed  CAS  Google Scholar 

  • Robichaud A, Stamatiou PB, Jin SL, Lachance N, MacDonald D, Laliberte F, Liu S, Huang Z, Conti M, Chan CC (2002) Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. J Clin Invest 110:1045–1052

    PubMed  CAS  Google Scholar 

  • Ron D, Chen CH, Caldwell J, Jamieson L, Orr E, Mochly-Rosen D (1994) Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. Proc Natl Acad Sci USA 91:839–843

    Article  PubMed  CAS  Google Scholar 

  • Scotland G, Houslay MD (1995) Chimeric constructs show that the unique N-terminal domain of the cyclic AMP phosphodiesterase RD1 (RNPDE4A1A; rPDE-IVA1) can confer membrane association upon the normally cytosolic protein chloramphenicol acetyltransferase. Biochem J 308(Pt 2):673–681

    PubMed  CAS  Google Scholar 

  • Sette C, Conti M (1996) Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. Involvement of serine 54 in the enzyme activation. J Biol Chem 271:16526–16534

    Article  PubMed  CAS  Google Scholar 

  • Seybold J, Newton R, Wright L, Finney PA, Suttorp N, Barnes PJ, Adcock IM, Giembycz MA (1998) Induction of phosphodiesterases 3B, 4A4, 4D1, 4D2, and 4D3 in Jurkat T-cells and in human peripheral blood T-lymphocytes by 8-bromo-cAMP and Gs-coupled receptor agonists. Potential role in beta2-adrenoreceptor desensitization. J Biol Chem 273: 20575–20588

    Article  PubMed  CAS  Google Scholar 

  • Shakur Y, Pryde JG, Houslay MD (1993) Engineered deletion of the unique N-terminal domain of the cyclic AMP-specific phosphodiesterase RD1 prevents plasma membrane association and the attainment of enhanced thermostability without altering its sensitivity to inhibition by rolipram. Biochem J 292(Pt 3):677–686

    PubMed  CAS  Google Scholar 

  • Shakur Y, Wilson M, Pooley L, Lobban M, Griffiths SL, Campbell AM, Beattie J, Daly C, Houslay MD (1995) Identification and characterization of the type-IVA cyclic AMP-specific phosphodiesterase RD1 as a membrane-bound protein expressed in cerebellum. Biochem J 306(Pt 3):801–809

    PubMed  CAS  Google Scholar 

  • Sharrocks AD, Yang SH, Galanis A (2000) Docking domains and substrate-specificity determination for MAP kinases. Trends Biochem Sci 25:448–453

    Article  PubMed  CAS  Google Scholar 

  • Shepherd MC, Baillie GS, Stirling DI, Houslay MD (2004) Remodelling of the PDE4 cAMP phosphodiesterase isoform profile upon monocyte-macrophage differentiation of human U937 cells. Br J Pharmacol 142:339–351

    Article  PubMed  CAS  Google Scholar 

  • Sikorski RS, Boguski MS, Goebl M, Hieter P (1990) A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60:307–317

    Article  PubMed  CAS  Google Scholar 

  • Smith KJ, Scotland G, Beattie J, Trayer IP, Houslay MD (1996) Determination of the structure of the N-terminal splice region of the cyclic AMP-specific phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and identification of the membrane association domain using chimeric constructs. J Biol Chem 271:16703–16711

    Article  PubMed  CAS  Google Scholar 

  • Smith FD, Langeberg LK, Scott JD (2006) The where’s and when’s of kinase anchoring. Trends Biochem Sci 31:316–323

    Article  PubMed  CAS  Google Scholar 

  • Smith KJ, Baillie GS, Hyde EI, Li X, Houslay TM, McCahill A, Dunlop AJ, Bolger GB, Klussmann E, Adams DR, Houslay MD (2007) 1H-NMR structural and functional characterisation of a cAMP-specific phosphodiesterase-4D5 (PDE4D5) N-terminal region peptide that disrupts PDE4D5 interaction with the signalling scaffold proteins, βarrestin and RACK1. Cell Signal 19:2612–2624

    Article  PubMed  CAS  Google Scholar 

  • Sondek J, Siderovski DP (2001) Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta-propeller scaffolding. Biochem Pharmacol 61:1329–1337

    Article  PubMed  CAS  Google Scholar 

  • Souness JE, Rao S (1997) Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases. Cell Signal 9:227–236

    Article  PubMed  CAS  Google Scholar 

  • Souness JE, Aldous D, Sargent C (2000) Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors. Immunopharmacology 47:127–162

    Article  PubMed  CAS  Google Scholar 

  • Steele MR, McCahill A, Thompson DS, MacKenzie C, Isaacs NW, Houslay MD, Bolger GB (2001) Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5. Cell Signal 13:507–513

    Article  PubMed  CAS  Google Scholar 

  • Stefan E, Wiesner B, Baillie GS, Mollajew R, Henn V, Lorenz D, Furkert J, Santamaria K, Nedvetsky P, Hundsrucker C, Beyermann M, Krause E, Pohl P, Gall I, MacIntyre AN, Bachmann S, Houslay MD, Rosenthal W, Klussmann E (2007) Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells. J Am Soc Nephrol 18:199–212

    Article  PubMed  CAS  Google Scholar 

  • Stehlik J, Movsesian MA (2006) Inhibitors of cyclic nucleotide phosphodiesterase 3 and 5 as therapeutic agents in heart failure. Expert Opin Investig Drugs 15:733–742

    Article  PubMed  CAS  Google Scholar 

  • Sturton G, Fitzgerald M (2002) Phosphodiesterase 4 inhibitors for the treatment of COPD. Chest 121:192S–196S

    Article  PubMed  CAS  Google Scholar 

  • Sullivan M, Olsen AS, Houslay MD (1999) Genomic organisation of the human cyclic AMP- specific phosphodiesterase PDE4C gene and its chromosomal localisation to 19p13.1, between RAB3A and JUND. Cell Signal 11:735–742

    Article  PubMed  CAS  Google Scholar 

  • Swinnen JV, Tsikalas KE, Conti M (1991) Properties and hormonal regulation of two structurally related cAMP phosphodiesterases from the rat Sertoli cell. J Biol Chem 266:18370–18377

    PubMed  CAS  Google Scholar 

  • Tasken K, Aandahl EM (2004) Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 84:137–167

    Article  PubMed  CAS  Google Scholar 

  • Tasken KA, Collas P, Kemmner WA, Witczak O, Conti M, Tasken K (2001) Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area. J Biol Chem 276:21999–22002

    Article  PubMed  CAS  Google Scholar 

  • Taylor SS, Kim C, Vigil D, Haste NM, Yang J, Wu J, Anand GS (2005) Dynamics of signaling by PKA. Biochim Biophys Acta 1754:25–37

    PubMed  CAS  Google Scholar 

  • Terasawa H, Kohda D, Hatanaka H, Tsuchiya S, Ogura K, Nagata K, Ishii S, Mandiyan V, Ullrich A, Schlessinger J et al (1994) Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos. Nat Struct Biol 1:891–897

    Article  PubMed  CAS  Google Scholar 

  • Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768–774

    Article  PubMed  CAS  Google Scholar 

  • Thornton C, Tang KC, Phamluong K, Luong K, Vagts A, Nikanjam D, Yaka R, Ron D (2004) Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization. J Biol Chem 279:31357–31364

    Article  PubMed  CAS  Google Scholar 

  • Uzawa S, Samejima I, Hirano T, Tanaka K, Yanagida M (1990) The fission yeast cut1+ gene regulates spindle pole body duplication and has homology to the budding yeast ESP1 gene. Cell 62: 913–925

    Article  PubMed  CAS  Google Scholar 

  • Vandecasteele G, Rochais F, Abi-Gerges A, Fischmeister R (2006) Functional localization of cAMP signalling in cardiac myocytes. Biochem Soc Trans 34:484–488

    Article  PubMed  CAS  Google Scholar 

  • Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin SL, Conti M (2001) Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase. J Biol Chem 276:11189–11198

    Article  PubMed  CAS  Google Scholar 

  • Vicini E, Conti M (1997) Characterization of an intronic promoter of a cyclic adenosine 3′,5′-monophosphate (cAMP)-specific phosphodiesterase gene that confers hormone and cAMP inducibility. Mol Endocrinol 11:839–850

    Article  PubMed  CAS  Google Scholar 

  • Wallace DA, Johnston LA, Huston E, MacMaster D, Houslay TM, Cheung YF, Campbell L, Millen JE, Smith RA, Gall I, Knowles RG, Sullivan M, Houslay MD (2005) Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene. Mol Pharmacol 67:1920–1934

    Article  PubMed  CAS  Google Scholar 

  • Wang P, Wu P, Ohleth KM, Egan RW, Billah MM (1999) Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils. Mol Pharmacol 56:170–174

    PubMed  CAS  Google Scholar 

  • Wang D, Deng C, Bugaj-Gaweda B, Kwan M, Gunwaldsen C, Leonard C, Xin X, Hu Y, Unterbeck A, De Vivo M (2003) Cloning and characterization of novel PDE4D isoforms PDE4D6 and PDE4D7. Cell Signal 15:883–891

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Peng M, Chen Y, Robinson H, Houslay MD, Cai J, Ke H (2007) Structures of the four sub-families of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem J 408:193–201

    Article  PubMed  CAS  Google Scholar 

  • Wong W, Scott JD (2004) AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 5:959–970

    Article  PubMed  CAS  Google Scholar 

  • Xiang Y, Naro F, Zoudilova M, Jin S, Conti M, Kobilka B (2005) Phosphodiesterase 4D is required for beta(2) adrenoceptor subtype-specific signaling in cardiac myocytes. Proc Natl Acad Sci USA 102:909–914

    Article  PubMed  CAS  Google Scholar 

  • Xu RX, Hassell AM, Vanderwall D, Lambert MH, Holmes WD, Luther MA, Rocque WJ, Milburn MV, Zhao Y, Ke H, Nolte RT (2000) Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. Science 288:1822–1825

    Article  PubMed  CAS  Google Scholar 

  • Xu RX, Rocque WJ, Lambert MH, Vanderwall DE, Luther MA, Nolte RT (2004) Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J Mol Biol 337:355–365

    Article  PubMed  CAS  Google Scholar 

  • Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D (2002) NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1. Proc Natl Acad Sci USA 99:5710–5715

    Article  PubMed  CAS  Google Scholar 

  • Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB (1999) The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform. J Biol Chem 274:14909–14917

    Article  PubMed  CAS  Google Scholar 

  • Yedovitzky M, Mochly-Rosen D, Johnson JA, Gray MO, Ron D, Abramovitch E, Cerasi E, Nesher R (1997) Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells. J Biol Chem 272:1417–1420

    Article  PubMed  CAS  Google Scholar 

  • Zaccolo M, Pozzan T (2002) Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes. Science 295:1711–1715

    Article  PubMed  CAS  Google Scholar 

  • Zeller E, Stief HJ, Pflug B, Sastre-y-Hernandez M (1984) Results of a phase II study of the antidepressant effect of rolipram. Pharmacopsychiatry 17:188–190

    Article  PubMed  CAS  Google Scholar 

  • Zhang HT, O’Donnell JM (2007) Phosphodiesterase-4 as a pharmacological target mediating antidepressant and cognitive effects on behavior. In: Beavo JA, Francis SH, Houslay MD (eds) Cyclic nucleotide phosphodiesterases in health and disease. CRC Press, Boca Raton, London, New York, pp 539–558

    Google Scholar 

  • Zhang J, Ma Y, Taylor SS, Tsien RY (2001) Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering. Proc Natl Acad Sci USA 98:14997–15002

    Article  PubMed  CAS  Google Scholar 

  • Zhang HT, Zhao Y, Huang Y, Dorairaj NR, Chandler LJ, O’Donnell JM (2004) Inhibition of the phosphodiesterase 4 (PDE4) enzyme reverses memory deficits produced by infusion of the MEK inhibitor U0126 into the CA1 subregion of the rat hippocampus. Neuropsychopharmacology 29:1432–1439

    Article  PubMed  CAS  Google Scholar 

  • Zhu J, Mix E, Winblad B (2001) The antidepressant and antiinflammatory effects of rolipram in the central nervous system. CNS Drug Rev 7:387–398

    PubMed  CAS  Google Scholar 

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  1. Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G128QQ, Scotland, UK

    A. C. McCahill, E. Huston, X. Li & M. D. Houslay

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  1. Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany

    Enno Klussmann

  2. The Vollum Institute, Oregon Health & Science University, Medical Research Bldg, Rm 322D 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA

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McCahill, A.C., Huston, E., Li, X., Houslay, M.D. (2008). PDE4 Associates with Different Scaffolding Proteins: Modulating Interactions as Treatment for Certain Diseases. In: Klussmann, E., Scott, J. (eds) Protein-Protein Interactions as New Drug Targets. Handbook of Experimental Pharmacology, vol 186. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-72843-6_6

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