PDE4 cAMP phosphodiesterases: Modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization

Biochemical Journal

Volumn 370, Issue 1, 2003, Pages 1-18

  Houslay, Miles D ^a   Adams, David R ^b  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b HERIOT WATT UNIVERSITY   (United Kingdom)

Author keywords

Arrestin; Asthma; Chronic obstructive pulmonary disease (COPD); Phosphorylation; Rolipram; Targeting

Indexed keywords

ACIDS; CATALYSTS; DEGRADATION;

ORCHESTRATE SIGNALLING;

ENZYMES;

CYCLIC AMP PHOSPHODIESTERASE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHODIESTERASE IV; PROTEIN TYROSINE KINASE; RECEPTOR; RETINA S ANTIGEN;

CATALYSIS; CELL COMPARTMENTALIZATION; DESENSITIZATION; ENZYME ACTIVITY; GENE; MOLECULAR INTERACTION; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; CATALYTIC DOMAIN; CELL COMPARTMENTATION; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; SIGNAL TRANSDUCTION;

EID: 0037443097     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20021698     Document Type: Review

References (130)

1. Houslay, M. D. and Milligan, G. (1997) Tailoring cAMP signalling responses through isoform multiplicity. Trends Biochem. Sci. 22, 217-224
2. Beavo, J. A. and Brunton, L. L. (2002) Cyclic nucleotide research; still expanding after half a century. Nat. Rev. Mol. Cell Biol. 3, 710-718
3. Colledge, M. and Scott, J. D. (1999) AKAPs: from structure to function. Trends Cell Biol. 9, 216-221
4. Rubin, C. S. (1994) A kinase anchor proteins and the intracellular targeting of signals carried by cAMP. Biochim. Biophys. Acta 1224, 467-479
5. de Rooij, J., Zwartkruis, F. J., Verheijen, M. H., Cool, R. H., Nijman, S. M., Wittinghofer, A. and Bos, J. L. (1998) EPAC is a Rap1 guanine-nucleotide-exchange factor directly activated by cAMP. Nature (London) 396, 474-477
6. Kawasaki, H., Springett, G. M., Mochizuki, N., Toki, M., Nakaya, M., Matsuda, M., Housman, D. E. and Graybiel, A. M. (1998) A family of cAMP-binding proteins that directly activate Rap1. Science 282, 2275-2279
7. Zaccolo, M. and Pozzan, T. (2002) Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes. Science 295, 1711-1715
8. Zhang, J., Ma, Y., Taylor, S. S. and Tsien, R. Y. (2001) Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering. Proc. Natl. Acad Sci. U.S.A. 98, 14997-15002
9. 2+ channels by β-adrenergic agonists. Proc. Natl. Acad. Sci. U.S.A. 93, 295-299
10. Rich, T. C., Fagan, K. A., Tse, T. E., Schaack, J., Cooper, D. M. and Karpen, J. W. (2001) A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell. Proc. Natl. Acad. Sci. U.S.A. 98, 13049-13054
11. Rich, T. C., Tse, T. E., Rohan, J. G., Schaack, J. and Karpen, J. W. (2001) In vivo assessment of local phosphodiesterase activity using tailored cyclic nucleotide-gated channels as cAMP sensors. J. Gen. Physiol. 118, 63-78
12. Diviani, D. and Scott, J. D. (2001) AKAP signaling complexes at the cytoskeleton. J. Cell. Sci. 114, 1431-1437
13. Houslay, M. D., Sullivan, M. and Bolger, G. B. (1998) The multi-enzyme PDE4 cAMP specific phosphodiesterase family: intracellular targeting, regulation and selective inhibition by compounds exerting anti-inflammatory and anti-depressant actions. Adv. Pharmacol. 44, 225-342
14. Houslay, M. D. (2001) PDE4 cAMP-specific phosphodiesterases. Prog. Nucleic Acid Res. Mol. Biol. 69, 249-315
15. Conti, M. and Jin, S. L. C. (1999) The molecular biology of cyclic nucleotide phosphodiesterases. Progr. Nucleic Acid Res. 63, 1-38
16. Manganiello, V. C. and Degerman, E. (1999) Cyclic nucleotide phosphodiesterases (PDEs): diverse regulators of cyclic nucleotide signals and inviting molecular targets for novel therapeutic agents. Thromb. Haemostasis 82, 407-411
17. Soderling, S. H. and Beavo, J. A. (2000) Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr. Opin. Cell Biol. 12, 174-179
18. Jin, C. L. and Conti, M. (2002) Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-α response. Proc. Natl. Acad. Sci. U.S.A. 99, 7628-7633
19. Hansen, G., Jin, S., Umetsu, D. T. and Conti, M. (2000) Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D. Proc. Natl. Acad. Sci. U.S.A. 97, 6751-6756
20. Spina, D., Landerls, L. J. and Page, C. P. (1998) The role of phosphodiesterase enzymes in allergy and asthma. Adv. Pharmacol. 44, 33-89
21. Palfreyman, M. N. (1995) Phosphodiesterase type IV inhibitors as antiinflammatory agents. Drugs Future 20, 793-804
22. Giembycz, M. A. (2000) Phosphodiesterase 4 inhibitors and the treatment of asthma: where are we now and where do we go from here? Drugs 59, 193-212
23. Torphy, T. J. (1998) Phosphodiesterase isozymes: molecular targets for novel antiasthma agents. Am. J. Respir. Crit. Care Med. 157, 351-370
24. Giembycz, M. A. (2002) Development status of second generation PDE4 inhibitors for asthma and COPD: the story so far. Monaldi Arch. Chest Dis. 57, 48-64
25. Huang, Z., Ducharme, Y., Macdonald, D. and Robichaud, A. (2001) The next generation of PDE4 inhibitors. Curr. Opin. Chem. Biol. 5, 432-438
26. Essayan, D. M. (1999) Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem. Pharmacol. 57, 965-973
27. Barnette, M. S. and Underwood, D. C. (2000) New phosphodiesterase inhibitors as therapeutics for the treatment of chronic lung disease. Curr. Opin. Pulm. Med. 6. 164-169
28. Schmidt, D., Dent, G. and Rabe, K. F. (1999) Selective phosphodiesterase inhibitors for the treatment of bronchial asthma and chronic obstructive pulmonary dizease. Clin. Exp. Allergy 29 (Suppl. 2), 99-109
29. Doherty, A. M. (1999) Phosphodiesterase 4 inhibitors as novel anti-inflammatory agents. Curr. Opin. Chem. Biol. 3, 466-473
30. Dousa, T. P. (1999) Cyclic-3′,5′-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney. Kidney Int. 55, 29-62
31. Burnouf, C. and Pruniaux, M. P. (2002) Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs. Curr. Pharm. Des. 8, 1255-1296
32. Zhang, H. T., Crissman, A. M., Dorairaj, N. R., Chandler, L. J. and O'Donnell, J. M. (2000) Inhibition of cAMP phosphodiesterase (PDE4) reverses memory deficits associated with NMDA receptor antagonism. Neuropsychopharmacology 23, 198-204
33. Zhang, H. T. and O'Donnell, J. M. (2000) Effects of rolipram on scopolamine-induced impairment of working and reference memory in the radial-arm maze tests in rats. Psychopharmacology (Berlin) 150, 311-316
34. O'Donnell, J. M. (1993) Antidepressant-like effects of rolipram and other inhibitors of cyclic adenosine monophosphate phosphodiesterase on behavior maintained by differential reinforcement of low response rate. J. Pharmacol. Exp. Ther. 264, 1168-1178
35. Marchmont, R. J. and Houslay, M. D. (1980) An intrinsic and a peripheral protein constitute the cAMP phosphodiesterase activity of rat liver plasma membranes. Biochem. J. 187, 381-392
36. Reeves, M. L., Leigh, B. K. and England, P. J. (1987) The identification of a new cyclic nucleotide phosphodiesterase activity in human and guinea-pig cardiac ventricle: implications for the mechanism of action of selective phosphodiesterase inhibitors. Biochem. J. 241, 535-541
37. Wachtel, H. (1982) Characteristic behavioural alterations in rats induced by rolipram and other selective cAMP phosphodiesterase inhibitors. Psychopharmacology 77, 309-314
38. Qiu, Y., Chen, C. N., Malone, T., Richter, L., Beckendorf, S. K. and Davis, R. L. (1991) Characterization of the memory gene dunce of Drosophila melanogaster. J. Mol. Biol. 222, 553-555
39. Davis, R. L., Takayasu, H., Eberwine, M. and Myres, J. (1989) Cloning and characterization of mammalian homologs of the Drosophila dunce+ gene. Proc. Natl. Acad. Sci. U.S.A. 86, 3604-3608
40. Swinnen, J. V., Joseph, D. R. and Conti, M. (1989) Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: Evidence for a family of genes. Proc. Natl. Acad. Sci. U.S.A. 86, 5325-5329
41. Bolger, G., Michaeli, T., Martins, T., St John, T., Steiner, B., Rodgers, L., Riggs, M., Wigler, M. and 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
42. Sullivan, M., Olsen, A. S. and Houslay, M. D. (1999) Genomic organization of the human cAMP specific phosphodiesterase PDE4C gene and its chromosomal localization to 19p13.1, between the genes for RAB3A and JUND. Cell. Signalling 11, 735-742
43. Davis, R. L. and Davidson, N. (1986) The memory gene dunce+ encodes a remarkable set of RNAs with internal heterogeneity. Mol. Cell. Biol. 6, 1464-1470
44. Vicini, E. and 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
45. Le Jeune, I. R., Shepherd, M., Van Heeke, G., Houslay, M. D. and Hall, I. P. (2002) cAMP-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
46. Rena, G., Begg, F., Ross, A., MacKenzie, C., McPhee, I., Campbell, L., Huston, E., Sullivan, M. and Houslay, M. D. (2001) Molecular cloning and characterization of the novel cAMP specific phosphodiesterase, PDE4A10. Mol. Pharmacol. 59, 996-1011
47. Horton, Y. M., Sullivan, M. and Houslay, M. D. (1995) Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19. Biochem. J. 308, 683-691
48. Beard, M. B., Olsen, A. E., Jones, R. E., Erdogan, S., Houslay, M. D. and Bolger, G. B. (2000) UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase (PDE4) family form a discrete module via electrostatic interactions. J. Biol. Chem. 275, 10349-10358
49. MacKenzie, S. J., Baillie, G. S., McPhee, I., Bolger, G. B. and Houslay, M. D. (2000) ERK2 MAP kinase binding, phosphorylation and regulation of PDE4D cAMP specific phosphodiesterases: the involvement of C-terminal docking sites and N-terminal UCR regions. J. Biol. Chem. 275, 16609-16617
50. Sette, C. and 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
51. Lim, J., Pahlke, G. and 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
52. m, rolipram-sensitive cAMP phosphodiesterase. Mapping of the catalytic domain. J. Biol. Chem. 267, 18929-18939
53. Beard, M. B., Huston, E., Campbell, L., Gall, I., McPhee, I., Yarwood, S., Scotland, G. and Houslay, M. D. (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 intracellufar targeting. Cell. Signalling 14, 453-465
54. Ekholm, D., Belfrage, P., Manganiello, V. and Degerman, E. (1997) Protein kinase A-dependent activation of PDE4 (cAMP-specific cyclic nucleotide phosphodiesterase) in cultured bovine vascular smooth muscle cells. Biochim. Biophys. Acta 1356, 64-70
55. Baillie, G., MacKenzie, S. J. and Houslay, M D. (2001) Phorbol 12-myristate 13-acetate triggers the protein kinase A-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
56. Sette, C., Iona, S. and Conti, M. (1994) The short-term activation of a rolipramsensitive, cAMP-specific phosphodiesterase by thyroid-stimulating hormone in thyroid FRTL-5 cells is mediated by a cAMP-dependent phosphorylation. J. Biol. Chem. 269, 9245-9252
57. Chang, Y. H., Conti, M., Lee, Y. C., Lai, H. L., Ching, Y. H. and Chern, Y. (1997) Activation of phosphodiesterase IV during desensitization of the A2A adenosine receptor-mediated cAMP response in rat pheochromocytoma (PC12) cells. J. Neurochem. 69, 1300-1309
58. Hoffmann, R., Wilkinson, I. R., McCallum, J. F., Engels, P. and Houslay, M. D. (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, 139-149
59. MacKenzie, S. J., Baillie, G. S., McPhee, I., MacKenzie, C., Seamons, R., McSorley, T., Millen, J., Beard, M. B., van Heeke, G. and Houslay, M. D. (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
60. Sette, C., Vicini, E. and Conti, M. (1994) The ratPDE3/IVd phosphodiesterase gene codes for multiple proteins differentially activated by cAMP-dependent protein kinase. J. Biol. Chem. 269, 18271-18274
61. Sette, C., Vicini, E. and Conti, M. (1994) Modulation of cellular responses by hormones: role of cAMP specific, rolipram-sensitive phosphodiesterases. Mol. Cell. Endocrinol. 100, 75-79
62. Laliberte, F., Liu, S., Gorseth, E., Bobechko, B., Bartlett, A., Lario, P., Gresser, M. J. and Huang, Z. (2002) In vitro PKA phosphorylation-mediated human PDE4A4 activation. FEBS Lett. 512, 205-208
63. Oki, N., Takahashi, S. I., Hidaka, H. and Conti, M. (2000) Short term feedback regulation of cAMP in FRTL-5 thyroid cells Role of pde4d3 phosphodiesterase activation. J. Biol. Chem. 275, 10831-10837
64. Xu, R. X., Hassell, A. M., Vanderwall, D., Lambert, M. H., Holmes, W. D., Luther, M. A., Rocque, W. J., Milburn, M. V., Zhao Y., Ke, H. and Nolte, R. T. (2000) Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. Science 266, 1822-1825
65. 2-adrenergic receptors by •-arrestins. Science 296, 834-836
66. Dodge, K. L., Khouangsathiene, S., Kapiloff, M. S., Mouton, R., Hill, E. V., Houslay, M. D., Langeberg, L. K. and Scott, J. D. (2001) mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J. 20, 1921-1930
67. Tasken, K. A., Collas, P., Kemmner, W. A., Witczak, O., Conti, M. and 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
68. m cAMP phosphodiesterase in rat fat cells by phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 67, 533-537
69. Murthy, K. S., Zhou, H. and Makhlouf, G. M. (2002) PKA-dependent activation of PDE3A and PDE4 and inhibition of adenyhte cyclase V/Vi in smooth muscle. Am. J. Physiol. Cell. Physiol. 262, C508-C517
70. Baillie, G. S., MacKenzie, S. J., McPhee, I and Houslay, M. D. (2000) Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cAMP-specific phosphodiesterases. Br. J. Pharmacol. 131, 811-819
71. Hoffmann, R., Baillie, G. S., MacKenzie, S. J., Yarwood, S. J. and Houslay, M. D. (1999) The MAP kinase ERK2 inhibits the cAMP-specific phosphodiesterase, HSPDE4D3 by phosphorylating it at Ser579. EMBO J. 18, 893-903
72. Sharrocks, A. D., Yang, S. H. and Galanis, A. (2000) Docking domains and substrate-specificity determination for MAP kinases. Trends Biochem. Sci. 25, 448-453
73. Houslay, M. D. and Kolch, W. (2000) Cell-type specific integration of cross-talk between extracellular signal-regulated kinase and cAMP signaling. Mol. Pharmacol. 58, 659-668
74. Liu, H. and Maurice, D. H. (1999) Phosphorylation-mediated activation and translocation of the cAMP-specific phosphodiesterase PDE4D3 by cAMP-dependent protein kinase and mitogen-activated protein kinases. A potential mechanism allowing for the coordinated regulation of PDE4D activity and targeting. J. Biol. Chem. 274, 10557-10565
75. Ahmad, F., Gao, G., Ling Mei, W., Landstrom, T. R., Degerman, E., Pierce, J. H. and Manganiello, V. C. (1999) IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells. J. Immunol. 162, 4864-4875
76. Verde, I., Pahlke, G., Salanova, M., Zhang, G., Wang, S., Coletti, D., Onuffer, J., Jin, S. L. and 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
77. Huston, E., Beard, M., McCallum, F., Pyne, N. J., Vandenabeele, P., Scotland, G. and Houslay, M. D. (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
78. McPhee, I., Yarwood, S. J., Huston, E., Scotland, G., Beard, M. B., Ross, A. H., Houslay, E. S. and Houslay, M. D. (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
79. O'Connell, J. C., McCallum, J. F., McPhee, I., Wakefield, J., Houslay, E. S., Wishart, W., Bolger, G., Frame, M. and Houslay, M. D. (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, 255-262
80. 2+-triggered membrane association with selectivity for interaction with phosphatidic acid. J. Biol. Chem. 277, 28298-28309
81. Scotland, G. and Houslay, M. D. (1995) Chimeric constructs show that the unique N-terminal domain of the cAMP phosphodiesterase RD1 (RNPDE4A1A; rPDE-IV(A1)) can confer membrane association upon the normally cytosolic protein chloramphenicol acetyltransferase. Biochem. J. 308, 673-681
82. Shakur, Y., Pryde, J. G. and Houslay, M. D. (1993) Engineered deletion of the unique N-terminal domain of the cAMP-specific phosphodiesterase RD1 prevents plasma membrane association and the attainment of enhanced thermostability without altering its sensitivity to inhibition by rolipram. Biochem. J. 292, 677-686
83. Smith, K. J., Scotland, G., Beattie, J., Trayer, I. P. and Houslay, M. D. (1996) Determination of the structure of the N-terminal splice region of the cAMP-specific phosphodiesterase RD1 (RNPDE4A1) by proton-NMR and identification of the membrane association domain using chimeric constructs. J. Biol. Chem. 271, 16703-16711
84. Exton, J. H. (1999) Regulation of phospholipase D. Biochim. Biophys. Acta 1439, 121-133
85. Hurley, J. H. and Misra, S. (2000) Signaling and subcellular targeting by membrane-binding domains. Annu. Rev. Biophys. Biomol. Struct. 29, 49-79
86. Hurley, J. H. and Meyer, T. (2001) Subcellular targeting by membrane lipids. Curr. Opin. Cell. Biol. 13, 146-152
87. DiSanto, M. E., Glaser, K. B. and Heaslip, R. J. (1995) Phospholipid regulation of a cAMP-specific phosphodiesterase (PDE4) from U937 cells. Cell. Signalling 7, 827-835
88. Marcoz, P., Nemoz, G., Prigent, A. F. and Lagarde, M. (1993) Phosphatidic acid stimulates the rolipram-sensitive cyclic nucleotide phosphodiesterase from rat thymocytes. Biochim. Biophys. Acta 1176, 129-136
89. Savany, A., Abriat, C., Nemoz, G., Lagarde, M. and Prigent, A. F. (1996) Activation of a cyclic nucleotide phosphodiesterase 4 (PDE4) from rat thymocytes by phosphatidic acid. Cell. Signalling 8, 511-516
90. El Bawab, S., Macovschi, O., Sette, C., Conti, M., Lagarde, M., Nemoz, G. and Prigent, A. F. (1997) Selective stimulation of a cAMP-specific phosphodiesterase (PDE4A5) isoform by phosphatidic acid molecular species endogenously formed in rat thymocytes. Eur. J. Biochem. 247, 1151-1157
91. Nemoz, G., Sette, C. and Conti, M. (1997) Selective activation of rolipram-sensitive, cAMP-specific phosphodiesterase isoforms by phosphatidic acid. Mol. Pharmacol. 51, 242-249
92. Ghosh, S., Strum, J. C., Sciorra, V. A., Daniel, L. and Bell, R. M. (1996) Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Rat-1 in 12-0-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells. J. Biol. Chem. 271, 8472-8480
93. Grange, M., Sette, C., Cuomo, M., Conti, M., Lagarde, M., Prigent, A. F. and Nemoz, G. (2000) The cAMP-specific phosphodiesterase PDE4D3 is regulated by phosphatidic acid binding: consequences for cAMP signaling pathway and characterization of a phosphatidic acid binding site. J. Biol. Chem. 275, 33379-33387
94. Luttrell, L. M. and Lefkowitz, R. J. (2002) The role of β-arrestins in the termination and transduction of G-protein-coupled receptor signals. J. Cell Sci. 115, 455-465
95. Murphy, B. J. and Scott, J. D. (1998) Functional anchoring of the cAMP-dependent protein kinase. Trends Cardiovasc. Med. 8, 89-95
96. Feliciello, A., Gottesman, M. E. and Avvedimento, E. V. (2001) The biological functions of A-kinase anchor proteins. J. Mol. Biol. 308, 99-114
97. Newlon, M. G., Roy, M., Morikis, D., Hausken, Z. E., Coghlan, V., Scott, J. D. and Jennings, P. A. (1999) The molecular basis for protein kinase A anchoring revealed by solution NMR. Nat. Struct. Biol. 6, 222-227
98. McCahill, A., Warwicker, J., Bolger, G. B., Houslay, M. D. and Yarwood, S. J. (2002) The RACK1 scaffold protein: a dynamic cog in cell response mechanisms. Mol. Pharmacol. 62, 1261-1272
99. Ron, D., Chen, C. H., Caldwell, J., Jamieson, L., Orr, E. and Mochly-Rosen, D. (1994) Cloning of an intracellular receptor for protein kinase C: a homolog of the β subunit of G proteins. Proc. Natl. Acad. Sci. U.S.A. 91, 839-843
100. Yarwood, S. J., Steele, M. R., Scotland, G., Houslay, M. D. and Bolger, G. B. (1999) The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform. J. Biol. Chem. 274, 14909-14917
101. Bolger, G. B., McCahill, A., Yarwood, S. J., Steele, M. S., Warwicker, J. and Houslay, M. D. (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
102. Steele, M. R., McCahill, A., Thompson, D. S., MacKenzie, C., Isaacs, N. W., Houslay, M. D. and Bolger, G. B. (2001) Identification of a surface on the β-propeller protein RACK1 that interacts with the cAMP specific phosphodiesterase PDE4D5. Cell. Signalling 13, 507-513
103. Pawson, T. (1995) Protein modules and signalling networks. Nature (London) 373, 573-580
104. Beard, M. B., O'Connell, J. C., Bolger, G. B. and Houslay, M. D. (1999) The unique N-terminal domain of the cAMP phosphodiesterase PDE4D4 allows for interaction with specific SH3 domains. FEBS Lett. 460, 173-177
105. MacKenzie, S. J., Yarwood, S. J., Peden, A. H., Bolger, G. B., Vernon, R. J. and Houslay, M. D. (1998) Stimulation of p70S6 kinase via a growth hormone controlled Pl-3 kinase pathway leads to the activation of a PDE4 cAMP specific phosphodiesterases in 3T3-F442A preadipocytes. Proc. Natl. Acad. Sci. U.S.A. 95, 3549-3554
106. Sullivan, M., Rena, G., Begg, F., Gordon, L., Olsen, A. S. and Houslay, M. D. (1998) Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2. Biochem. J. 333, 693-703
107. Souness, J. E. and Rao, S. (1997) Proposal for pharmacologically distinct conformers of PDE4. Cell. Signalling 9, 227-236
108. Shakur, Y., Wilson, M., Pooley, L., Lobban, M., Griffiths, S. L., Campbell, A. M., Beattie, J., Daly, C. and Houslay, M. D. (1995) Identification and characterization of the type-IVA cAMP-specific phosphodiesterase RD1 as a membrane-bound protein expressed in cerebellum. Biochem. J. 306, 801-809
109. Bolger, G. B., Rodgers, L. and Riggs, M. (1994) Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases. Gene 149, 237-244
110. Zhan, C. G. and Zheng, F. (2001) First computational evidence for a catalytic bridging hydroxide ion in a phosphodiesterase active site. J. Am. Chem. Soc. 123, 2835-2838
111. Francis, S. H., Colbran, J. L., McAllister Lucas, L. M. and Corbin, J. D. (1994) Zinc interactions and conserved motils of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase. J. Biol. Chem. 269, 22477-22480
112. Londesborough, J. (1985) Evidence that the peripheral cAMP phosphodiesterase of rat liver plasma membranes is a metalloenzyme. Biochem. J. 225, 143-147
113. Wilkinson, I., Engels, P. and Houelay, M. D. (1997) Rolipram inhibition of the human cAMP phosphodiesterase splice variant HSPDE4D3 expressed in yeast (S. cerevisiae). Pharmacol. Rev. Commun. 9, 215-226
114. Huston, E., Lumb, S., Russell, A., Catterall, C., Ross, A. H., Steele, M. R., Bolger, G. B., Perry, M., Owens, R. and Houslay, M. D. (1997) Molecular cloning and transient expression in C0S7 cells of a novel human PDE4B cAMP specific phosphodiesterase, HSPDE4B3. Biochem. J. 328, 549-558
115. Bolger, G. B., Erdogan, S., Jones, R. E., Loughney, K., Scotland, G., Hoffmann, R., Wilkinson, I., Farrell, C. and Houslay, M. D. (1997) Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene. Biochem. J. 328, 539-548
116. McPhee, I., Pooley, L., Lobban, M., Bolger, G. and Houslay, M. D. (1995) Identification, characterization and regional distribution in brain of RPDE-6 (RNPDE4A5), a novel splice variant of the PDE4A cAMP phosphodiesterase family. Biochem. J. 310, 965-974
117. Jacobitz, S., McLaughlin, M. M., Livi, G. P., Burman, M. and Torphy, T. J. (1996) Mapping the functional domains of human recombinant phosphodiesterase 4A: structural requirements for catalytic activity and rolipram binding. Mol. Pharmacol. 50, 891-899
118. Owens, R. J., Catterall, C., Batty, D., Jappy, J., Russell, A., Smith, B., O'Connell, J. and Perry, M. (1997) Human phosphodiesterase 4A: characterization of full length and truncated enzymes expressed in COS cells. Biochem. J. 326, 53-60
119. Dym, O., Xenarios, I., Ke, H. and Colicelli, J. (2002) Molecular docking of competitive phosphodiesterase inhibitors. Mol. Pharmacol. 61, 20-25
120. Richter, W., Unciuleac, L., Hermsdorf, T., Kronbach, T. and Dettmer, D. (2001) Identification of substrate specificity determinants in human cAMP-specific phosphodiesterase 4A by single-point mutagenesis. Cell. Signalling 13, 159-167
121. Herman, S. B., Juilfs, D. M., Fauman, E. B., Juneau, P. and Menetski, J. P. (2000) Analysis of a mutation in phosphodiesterase type 4 that alters both inhibitor activity and nucleotide selectivity. Mol. Pharmacol. 57, 991-999
122. Richter, W., Unciuleac, L., Hermsdorf, T., Kronbach, T. and Dettmer, D. (2001) Identification of inhibitor binding sites of the cAMP-specific phosphodiesterase 4. Cell. Signalling 13, 287-297
123. Liu, S., Laliberte, F., Bobechko, B., Bartlett, A., Lario, P., Gorseth, E., Van Hamme, J., Gresser, M. J. and Huang, Z. (2001) Dissecting the cofactor-dependent and independent bindings of PDE4 inhibitors. Biochemistry 40, 10179-10186
124. Laliberte, F., Han, Y., Govindarajan, A., Giroux, A., Liu, S., Bobechko, B., Lario, P., Bartlett, A., Gorseth, E., Gresser, M. and Huang, Z. (2000) Conformational difference between PDE4 apoenzyme and holoenzyme. Biochemistry 39, 6449-6458
125. Lee, M. E., Markowitz, J., Lee, J. O. and Lee, H. (2002) Crystal structure of phosphodiesterase 4D and inhibitor complex. FEBS Lett. 530, 53-58
126. Kovala, T., Sanwal, B. D. and Ball, E. H. (1997) Recombinant expression of a type IV, cAMP-specific phosphodiesterase: characterization and structure-function studies of deletion mutants. Biochemistry 36, 2968-2976
127. Rocque, W., Holmes, W., Patel, I., Doughertf, R, Ittoop, O., Overran, L., Hoffman, C., Wizely, G., Willard, D. and Luther, M. (1997) Detailed characterization of a purified type 4 phosphodiesterase, HSPDE4B2B: differentiation of high and low affinity (R)-rolipram binding. Protein Expression Purif. 9, 191-202
128. Rocque, W. J., Tian, G., Wizeman, J. S., Holmes, W. D., Zajac-Thompson, I., Willard, D. H., Patel, I. R., Wizely, G. B., Clay, W.C. Kadwell, S. H. et al. (1997) Human recombinant phosphodiesterase 4B2B binds (R)-rolipram at a single site with two affinities. Biochemistry 36, 14250-14261
129. Richter, W. and 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
130. MacKenzie, S. J. and Houslay, M. D. (2000) The action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of CREB and p38 MAP kinase in U937 monocytic cells. Biochem. J 347, 571-578