This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by CONTI, M. Articles by VICINI, E. Search for Related Content PubMed PubMed Citation Articles by CONTI, M. Articles by VICINI, E.

Recent Progress in Understanding the Hormonal Regulation of Phosphodiesterases

Department of Gynecology and Obstetrics, Division of Reproductive Biology, Stanford University Medical Center Stanford, California 94305-5317

Correspondence: Address reprint requests to: Marco Conti, M.D., Department of Gynecology and Obstetrics, Division of Reproductive Biology, Stanford University Medical Center, 300 Pasteur Drive, Room A344, Stanford, California 94305-5317.

Abstract

I. Introduction: LAYER after layer of novel regulatory circuits have been added to the map charting the signal transduction pathways that transport information throughout the cell. New components of these pathways are found at a breathtaking pace, and new functions for old components are continuously uncovered. It is now recognized that the complexity of these pathways resembles the intricacy and integration of the pathways of intermediate metabolism. This is especially true for the cyclic nucleotide-dependent signal transduction and its components, including cyclic nucleotide phosphodiesterases (PDEs).These are the enzymes that with cyclases control the intracellular concentration of cyclic nucleotides. With the development of new molecular tools, a wealth of new information has accumulated on the structure and function of these enzymes. Four years ago we reviewed the current knowledge on the mechanisms of hormonal regulation of PDEs (1). Here, we update this survey, reporting the most recent developments of this field. Since our previous review, many primary structures of the human and mammalian PDEs have been elucidated. This has brought about a better understanding of the structure/function relationship of these proteins. Furthermore, PDE gene structure is being actively investigated, adding a further dimension to the regulation of these enzymes and opening new avenues of investigation. Novel mechanisms of regulation have been uncovered, linking these enzymes to new hormone-dependent functions. As we will discuss in detail, the overall picture derived from these findings reinforces the concept that PDEs may serve three major functions in the cell target for hormones and neurotransmitters: 1) They are effectors in signal transduction, 2) they play a role in integrating different signal transduction pathways, and 3) they may also serve as a dampening device to decrease or terminate hormonal stimulation.

This article has been cited by other articles:

				M. D. Bruss, W. Richter, K. Horner, S.-L. C. Jin, and M. Conti Critical Role of PDE4D in {beta}2-Adrenoceptor-dependent cAMP Signaling in Mouse Embryonic Fibroblasts J. Biol. Chem., August 15, 2008; 283(33): 22430 - 22442. [Abstract] [Full Text] [PDF]

				K. A. Neville, S. J. Szefler, S. M. Abdel-Rahman, G. Lahu, K. Zech, R. Herzog, T. D. Bethke, M. C. Gleason, and G. L. Kearns Single-Dose Pharmacokinetics of Roflumilast in Children and Adolescents J. Clin. Pharmacol., August 1, 2008; 48(8): 978 - 985. [Abstract] [Full Text] [PDF]

				M.-L. Wong, F. Whelan, P. Deloukas, P. Whittaker, M. Delgado, R. M. Cantor, S. M. McCann, and J. Licinio Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response PNAS, October 10, 2006; 103(41): 15124 - 15129. [Abstract] [Full Text] [PDF]

				J. Cheng, M. A. Thompson, H. J. Walker, C. E. Gray, G. M. Warner, W. Zhou, and J. P. Grande Lixazinone stimulates mitogenesis of madin-darby canine kidney cells. Experimental Biology and Medicine, March 1, 2006; 231(3): 288 - 295. [Abstract] [Full Text] [PDF]

				S. Wang, G. Wang, B. E. Barton, T. F. Murphy, and H. F. S. Huang Impaired Sperm Function After Spinal Cord Injury in the Rat Is Associated With Altered Cyclic Adenosine Monophosphate Signaling J Androl, September 1, 2005; 26(5): 592 - 600. [Abstract] [Full Text] [PDF]

				J. Seybold, D. Thomas, M. Witzenrath, S. Boral, A. C. Hocke, A. Burger, A. Hatzelmann, H. Tenor, C. Schudt, M. Krull, et al. Tumor necrosis factor-{alpha}-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability Blood, May 1, 2005; 105(9): 3569 - 3576. [Abstract] [Full Text] [PDF]

				Y. Xiang, F. Naro, M. Zoudilova, S.-L. C. Jin, M. Conti, and B. Kobilka Phosphodiesterase 4D is required for {beta}2 adrenoceptor subtype-specific signaling in cardiac myocytes PNAS, January 18, 2005; 102(3): 909 - 914. [Abstract] [Full Text] [PDF]

				H. Yoshida, L. Beltran-Parrazal, P. Butler, M. Conti, A. C. Charles, and R. I. Weiner Lowering Cyclic Adenosine-3',5'-Monophosphate (cAMP) Levels by Expression of a cAMP-Specific Phosphodiesterase Decreases Intrinsic Pulsatile Gonadotropin-Releasing Hormone Secretion from GT1 Cells Mol. Endocrinol., October 1, 2003; 17(10): 1982 - 1990. [Abstract] [Full Text] [PDF]

				D. H. Maurice, D. Palmer, D. G. Tilley, H. A. Dunkerley, S. J. Netherton, D. R. Raymond, H. S. Elbatarny, and S. L. Jimmo Cyclic Nucleotide Phosphodiesterase Activity, Expression, and Targeting in Cells of the Cardiovascular System Mol. Pharmacol., September 1, 2003; 64(3): 533 - 546. [Abstract] [Full Text] [PDF]

				V. Fournier, P. Leclerc, N. Cormier, and J. L. Bailey Implication of Calmodulin-Dependent Phosphodiesterase Type 1 During Bovine Sperm Capacitation J Androl, January 1, 2003; 24(1): 104 - 112. [Abstract] [Full Text] [PDF]

				S. Oger, C. Mehats, E. Dallot, F. Ferre, and M.-J. Leroy Interleukin-1{beta} Induces Phosphodiesterase 4B2 Expression in Human Myometrial Cells through a Prostaglandin E2- and Cyclic Adenosine 3',5'-Monophosphate-Dependent Pathway J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5524 - 5531. [Abstract] [Full Text] [PDF]

				W. Richter and M. Conti Dimerization of the Type 4 cAMP-specific Phosphodiesterases Is Mediated by the Upstream Conserved Regions (UCRs) J. Biol. Chem., October 18, 2002; 277(43): 40212 - 40221. [Abstract] [Full Text] [PDF]

				I. R. Le Jeune, M. Shepherd, G. Van Heeke, M. D. Houslay, and I. P. Hall 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., September 20, 2002; 277(39): 35980 - 35989. [Abstract] [Full Text] [PDF]

				Y. J. Chiu and I. A. Reid Effect of Sildenafil on Renin Secretion in Human Subjects Experimental Biology and Medicine, September 1, 2002; 227(8): 620 - 625. [Abstract] [Full Text] [PDF]

				C. Mehats, G. Tanguy, E. Dallot, D. Cabrol, F. Ferre, and M.-J. Leroy Is Up-Regulation of Phosphodiesterase 4 Activity by PGE2 Involved in the Desensitization of {beta}-Mimetics in Late Pregnancy Human Myometrium? J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5358 - 5365. [Abstract] [Full Text] [PDF]

				L. Persani, S. Borgato, A. Lania, M. Filopanti, G. Mantovani, M. Conti, and A. Spada Relevant cAMP-Specific Phosphodiesterase Isoforms in Human Pituitary: Effect of Gs{alpha} Mutations J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3795 - 3800. [Abstract] [Full Text] [PDF]

				R. T. Schermuly, N. Weissmann, B. Enke, H. A. Ghofrani, W. G. Forssmann, F. Grimminger, W. Seeger, and D. Walmrath Urodilatin, a Natriuretic Peptide Stimulating Particulate Guanylate Cyclase, and the Phosphodiesterase 5 Inhibitor Dipyridamole Attenuate Experimental Pulmonary Hypertension . Synergism upon Coapplication Am. J. Respir. Cell Mol. Biol., August 1, 2001; 25(2): 219 - 225. [Abstract] [Full Text] [PDF]

				T. C. Rich, T. E. Tse, J. G. Rohan, J. Schaack, and J. W. Karpen In Vivo Assessment of Local Phosphodiesterase Activity Using Tailored Cyclic Nucleotide-Gated Channels as Camp Sensors J. Gen. Physiol., July 1, 2001; 118(1): 63 - 78. [Abstract] [Full Text] [PDF]

				P. F. Pollice, R. N. Rosier, R. J. Looney, J. E. Puzas, E. M. Schwarz, and R. J. O'Keefe Oral Pentoxifylline Inhibits Release of Tumor Necrosis Factor-Alpha from Human Peripheral Blood Monocytes : A Potential Treatment for Aseptic Loosening of Total Joint Components J. Bone Joint Surg. Am., July 1, 2001; 83(7): 1057 - 1061. [Abstract] [Full Text] [PDF]

				G. A. Piazza, W. J. Thompson, R. Pamukcu, H. W. Alila, C. M. Whitehead, L. Liu, J. R. Fetter, W. E. Gresh Jr., A. J. Klein-Szanto, D. R. Farnell, et al. Exisulind, a Novel Proapoptotic Drug, Inhibits Rat Urinary Bladder Tumorigenesis Cancer Res., May 1, 2001; 61(10): 3961 - 3968. [Abstract] [Full Text]

				S. Stricker and T. Smythe 5-HT causes an increase in cAMP that stimulates, rather than inhibits, oocyte maturation in marine nemertean worms Development, January 4, 2001; 128(8): 1415 - 1427. [Abstract] [PDF]

				M. Conti Phosphodiesterases and Cyclic Nucleotide Signaling in Endocrine Cells Mol. Endocrinol., September 1, 2000; 14(9): 1317 - 1327. [Full Text]

				L. Persani, A. Lania, L. Alberti, R. Romoli, G. Mantovani, S. Filetti, A. Spada, and M. Conti Induction of Specific Phosphodiesterase Isoforms by Constitutive Activation of the cAMP Pathway in Autonomous Thyroid Adenomas J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2872 - 2878. [Abstract] [Full Text]

				G. Hansen, S.-L. C. Jin, D. T. Umetsu, and M. Conti Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D PNAS, June 6, 2000; 97(12): 6751 - 6756. [Abstract] [Full Text] [PDF]

				S. J. MacKenzie, G. S. Baillie, I. McPhee, G. B. Bolger, and M. D. Houslay 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., May 26, 2000; 275(22): 16609 - 16617. [Abstract] [Full Text] [PDF]

				F. Ahmad, L.-N. Cong, L. Stenson Holst, L.-M. Wang, T. Rahn Landstrom, J. H. Pierce, M. J. Quon, E. Degerman, and V. C. Manganiello Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells J. Immunol., May 1, 2000; 164(9): 4678 - 4688. [Abstract] [Full Text] [PDF]

				N. Oki, S.-I. Takahashi, H. Hidaka, and M. Conti Short Term Feedback Regulation of cAMP in FRTL-5 Thyroid Cells. ROLE OF PDE4D3 PHOSPHODIESTERASE ACTIVATION J. Biol. Chem., April 6, 2000; 275(15): 10831 - 10837. [Abstract] [Full Text] [PDF]

				R. T. Schermuly, A. Roehl, N. Weissmann, H. A. Ghofrani, C. Schudt, H. Tenor, F. Grimminger, W. Seeger, and D. Walmrath Subthreshold Doses of Specific Phosphodiesterase Type 3 and 4 Inhibitors Enhance the Pulmonary Vasodilatory Response to Nebulized Prostacyclin with Improvement in Gas Exchange J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 512 - 520. [Abstract] [Full Text]

				C. Méhats, G. Tanguy, B. Paris, B. Robert, N. Pernin, F. Ferré, and M.-J. Leroy Pregnancy Induces a Modulation of the cAMP Phosphodiesterase 4-Conformers Ratio in Human Myometrium: Consequences for the Utero-Relaxant Effect of PDE4-Selective Inhibitors J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 817 - 823. [Abstract] [Full Text]

				A. Aversa, F. Mazzilli, T. Rossi, M. Delfino, A. M. Isidori, and A. Fabbri Effects of sildenafil (ViagraTM) administration on seminal parameters and post-ejaculatory refractory time in normal males Hum. Reprod., January 1, 2000; 15(1): 131 - 134. [Abstract] [Full Text] [PDF]

				T. L. Fink, S. H. Francis, A. Beasley, K. A. Grimes, and J. D. Corbin Expression of an Active, Monomeric Catalytic Domain of the cGMP-binding cGMP-specific Phosphodiesterase (PDE5) J. Biol. Chem., December 3, 1999; 274(49): 34613 - 34620. [Abstract] [Full Text] [PDF]

				F. Naro, C. Sette, E. Vicini, V. De Arcangelis, M. Grange, M. Conti, M. Lagarde, M. Molinaro, S. Adamo, and G. Némoz Involvement of Type 4 cAMP-Phosphodiesterase in the Myogenic Differentiation of L6 Cells Mol. Biol. Cell, December 1, 1999; 10(12): 4355 - 4367. [Abstract] [Full Text]

				R. T. SCHERMULY, H. A. GHOFRANI, B. ENKE, N. WEISSMANN, F. GRIMMINGER, W. SEEGER, C. SCHUDT, and D. WALMRATH Low-dose Systemic Phosphodiesterase Inhibitors Amplify the Pulmonary Vasodilatory Response to Inhaled Prostacyclin in Experimental Pulmonary Hypertension Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1500 - 1506. [Abstract] [Full Text]

				S.-L. C. Jin, F. J. Richard, W.-P. Kuo, A. J. D'Ercole, and M. Conti Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice PNAS, October 12, 1999; 96(21): 11998 - 12003. [Abstract] [Full Text] [PDF]

				I. J. Gonzalez-Robayna, T. N. Alliston, P. Buse, G. L. Firestone, and J. S. Richards Functional and Subcellular Changes in the A-Kinase-Signaling Pathway: Relation to Aromatase and Sgk Expression during the Transition of Granulosa Cells to Luteal Cells Mol. Endocrinol., August 1, 1999; 13(8): 1318 - 1337. [Abstract] [Full Text]

				W. Richter, D. Dettmer, and H.-J. Glander Detection of mRNA transcripts of cyclic nucleotide phosphodiesterase subtypes in ejaculated human spermatozoa Mol. Hum. Reprod., August 1, 1999; 5(8): 732 - 736. [Abstract] [Full Text] [PDF]

				M. Côté, M. D. Payet, E. Rousseau, G. Guillon, and N. Gallo-Payet Comparative Involvement of Cyclic Nucleotide Phosphodiesterases and Adenylyl Cyclase on Adrenocorticotropin-Induced Increase of Cyclic Adenosine Monophosphate in Rat and Human Glomerulosa Cells Endocrinology, August 1, 1999; 140(8): 3594 - 3601. [Abstract] [Full Text]

				J. Lim, G. Pahlke, and M. Conti Activation of the cAMP-specific Phosphodiesterase PDE4D3 by Phosphorylation. IDENTIFICATION AND FUNCTION OF AN INHIBITORY DOMAIN J. Biol. Chem., July 9, 1999; 274(28): 19677 - 19685. [Abstract] [Full Text] [PDF]

				Y. J. Chiu, S.-H. Hu, and I. A. Reid Inhibition of Phosphodiesterase III with Milrinone Increases Renin Secretion in Human Subjects J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 16 - 19. [Abstract] [Full Text]

				C. Méhats, G. Tanguy, E. Dallot, B. Robert, R. Rebourcet, F. Ferré, and M. J. Leroy Selective Up-Regulation of Phosphodiesterase-4 Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Specific Phosphodiesterase Variants by Elevated cAMP Content in Human Myometrial Cells in Culture Endocrinology, July 1, 1999; 140(7): 3228 - 3237. [Abstract] [Full Text]

				J. D. Corbin and S. H. Francis Cyclic GMP Phosphodiesterase-5: Target of Sildenafil J. Biol. Chem., May 14, 1999; 274(20): 13729 - 13732. [Full Text] [PDF]

				M. Salanova, S.-Y. Chun, S. Iona, C. Puri, M. Stefanini, and M. Conti Type 4 Cyclic Adenosine Monophosphate-Specific Phosphodiesterases Are Expressed in Discrete Subcellular Compartments during Rat Spermiogenesis Endocrinology, May 1, 1999; 140(5): 2297 - 2306. [Abstract] [Full Text]

				I. McPhee, S. J. Yarwood, G. Scotland, E. Huston, M. B. Beard, A. H. Ross, E. S. Houslay, and M. D. Houslay 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., April 23, 1999; 274(17): 11796 - 11810. [Abstract] [Full Text] [PDF]

				F. Ahmad, G. Gao, L. M. Wang, T. R. Landstrom, E. Degerman, J. H. Pierce, and V. C. Manganiello IL-3 and IL-4 Activate Cyclic Nucleotide Phosphodiesterases 3 (PDE3) and 4 (PDE4) by Different Mechanisms in FDCP2 Myeloid Cells J. Immunol., April 15, 1999; 162(8): 4864 - 4875. [Abstract] [Full Text] [PDF]

				A. Ibrahimi, N. Abumrad, H. Maghareie, M. Golia, I. Shoshani, L. Desaubry, and R. A. Johnson Adenylyl cyclase P-site ligands accelerate differentiation in Ob1771 preadipocytes Am J Physiol Cell Physiol, February 1, 1999; 276(2): C487 - C496. [Abstract] [Full Text] [PDF]

				M. Takahashi, R. Terwilliger, C. Lane, P. S. Mezes, M. Conti, and R. S. Duman Chronic Antidepressant Administration Increases the Expression of cAMP-Specific Phosphodiesterase 4A and 4B Isoforms J. Neurosci., January 15, 1999; 19(2): 610 - 618. [Abstract] [Full Text] [PDF]

				P. Ma, S. Wera, P. Van Dijck, and J. M. Thevelein The PDE1-encoded Low-Affinity Phosphodiesterase in the Yeast Saccharomyces cerevisiae Has a Specific Function in Controlling Agonist-induced cAMP Signaling Mol. Biol. Cell, January 1, 1999; 10(1): 91 - 104. [Abstract] [Full Text]

				K. L. O'Connor, L. M. Shaw, and A. M. Mercurio Release of cAMP Gating by the {alpha}6{beta}4 Integrin Stimulates Lamellae Formation and the Chemotactic Migration of Invasive Carcinoma Cells J. Cell Biol., December 14, 1998; 143(6): 1749 - 1760. [Abstract] [Full Text] [PDF]

				F. A. Antoni, M. Palkovits, J. Simpson, S. M. Smith, A. L. Leitch, R. Rosie, G. Fink, and J. M. Paterson Ca2+/Calcineurin-Inhibited Adenylyl Cyclase, Highly Abundant in Forebrain Regions, Is Important for Learning and Memory J. Neurosci., December 1, 1998; 18(23): 9650 - 9661. [Abstract] [Full Text] [PDF]

				J. Seybold, R. Newton, L. Wright, P. A. Finney, N. Suttorp, P. J. Barnes, I. M. Adcock, and M. A. Giembycz 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 beta 2-ADRENORECEPTOR DESENSITIZATION J. Biol. Chem., August 7, 1998; 273(32): 20575 - 20588. [Abstract] [Full Text] [PDF]

				T. M. Moore, P. M. Chetham, J. J. Kelly, and T. Stevens Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP Am J Physiol Lung Cell Mol Physiol, August 1, 1998; 275(2): L203 - L222. [Abstract] [Full Text] [PDF]

				S.-L. C. Jin, T. Bushnik, L. Lan, and M. Conti Subcellular Localization of Rolipram-sensitive, cAMP-specific Phosphodiesterases. DIFFERENTIAL TARGETING AND ACTIVATION OF THE SPLICING VARIANTS DERIVED FROM THE PDE4D GENE J. Biol. Chem., July 31, 1998; 273(31): 19672 - 19678. [Abstract] [Full Text] [PDF]

				A. Lania, L. Persani, E. Ballaré, S. Mantovani, M. Losa, and A. Spada Constitutively Active Gs{alpha} Is Associated with an Increased Phosphodiesterase Activity in Human Growth Hormone-Secreting Adenomas J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1624 - 1628. [Abstract] [Full Text]

				S. J. MacKenzie, S. J. Yarwood, A. H. Peden, G. B. Bolger, R. G. Vernon, and M. D. Houslay Stimulation of p70S6 kinase via a growth hormone-controlled phosphatidylinositol 3-kinase pathway leads to the activation of a PDE4A cyclic AMP-specific phosphodiesterase in 3T3-F442A preadipocytes PNAS, March 31, 1998; 95(7): 3549 - 3554. [Abstract] [Full Text] [PDF]

				S. Iona, M. Cuomo, T. Bushnik, F. Naro, C. Sette, M. Hess, E. R. Shelton, and M. Conti Characterization of the Rolipram-Sensitive, Cyclic AMP-Specific Phosphodiesterases: Identification and Differential Expression of Immunologically Distinct Forms in the Rat Brain Mol. Pharmacol., January 1, 1998; 53(1): 23 - 32. [Abstract] [Full Text]

				C. J. Smith, R. Huang, D. Sun, S. Ricketts, C. Hoegler, J.-Z. Ding, R. A. Moggio, and T. H. Hintze Development of Decompensated Dilated Cardiomyopathy Is Associated With Decreased Gene Expression and Activity of the Milrinone-Sensitive cAMP Phosphodiesterase PDE3A Circulation, November 4, 1997; 96(9): 3116 - 3123. [Abstract] [Full Text]

				R. S. Wagner, C. J. Smith, A. M. Taylor, and R. A. Rhoades Phosphodiesterase Inhibition Improves Agonist-Induced Relaxation of Hypertensive Pulmonary Arteries J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1650 - 1657. [Abstract] [Full Text]

				M. Lamas and P. Sassone-Corsi The Dynamics of the Transcriptional Response to Cyclic Adenosine 3',5'-Monophosphate: Recurrent Inducibility and Refractory Phase Mol. Endocrinol., September 1, 1997; 11(10): 1415 - 1424. [Abstract] [Full Text]

				E. Vicini and M. Conti Characterization of an Intronic Promoter of a Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Specific Phosphodiesterase Gene that Confers Hormone and cAMP Inducibility Mol. Endocrinol., June 1, 1997; 11(7): 839 - 850. [Abstract] [Full Text]

				C. C.S. Chini, J. P. Grande, E. N. Chini, and T. P. Dousa Compartmentalization of cAMP Signaling in Mesangial Cells by Phosphodiesterase Isozymes PDE3 and PDE4. REGULATION OF SUPEROXIDATION AND MITOGENESIS J. Biol. Chem., April 11, 1997; 272(15): 9854 - 9859. [Abstract] [Full Text] [PDF]

				D. M. Juilfs, H.-J. Fulle, A. Z. Zhao, M. D. Houslay, D. L. Garbers, and J. A. Beavo A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway PNAS, April 1, 1997; 94(7): 3388 - 3395. [Abstract] [Full Text] [PDF]

				E. Degerman, P. Belfrage, and V. C. Manganiello Structure, Localization, and Regulation of cGMP-inhibited Phosphodiesterase (PDE3) J. Biol. Chem., March 14, 1997; 272(11): 6823 - 6826. [Full Text] [PDF]

				J. B. Cheng, J. W. Watson, C. J. Pazoles, J. D. Eskra, R. J. Griffiths, V. L. Cohan, C. R. Turner, H. J. Showell, and E. R. Pettipher The Phosphodiesterase Type 4 (PDE4) Inhibitor CP-80,633 Elevates Plasma Cyclic AMP Levels and Decreases Tumor Necrosis Factor-alpha (TNFalpha ) Production in Mice: Effect of Adrenalectomy J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 621 - 626. [Abstract] [Full Text]

				T. J. TORPHY Phosphodiesterase Isozymes . Molecular Targets for Novel Antiasthma Agents Am. J. Respir. Crit. Care Med., February 1, 1997; 157(2): 351 - 370. [Full Text]

				G. Nemoz, C. Sette, and M. Conti Selective Activation of Rolipram-Sensitive, cAMP-Specific Phosphodiesterase Isoforms by Phosphatidic Acid Mol. Pharmacol., February 1, 1997; 51(2): 242 - 249. [Abstract] [Full Text] [PDF]

				C. E. Poteet-Smith, J. B. Shabb, S. H. Francis, and J. D. Corbin Identification of Critical Determinants for Autoinhibition in the Pseudosubstrate Region of Type Ialpha cAMP-dependent Protein Kinase J. Biol. Chem., January 3, 1997; 272(1): 379 - 388. [Abstract] [Full Text] [PDF]

				E. Huston, L. Pooley, P. Julien, G. Scotland, I. McPhee, M. Sullivan, G. Bolger, and M. D. Houslay 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., December 6, 1996; 271(49): 31334 - 31344. [Abstract] [Full Text] [PDF]

				C. Sette and M. Conti Phosphorylation and Activation of a cAMP-specific Phosphodiesterase by the cAMP-dependent Protein Kinase. INVOLVEMENT OF SERINE 54IN THE ENZYME ACTIVATION J. Biol. Chem., July 12, 1996; 271(28): 16526 - 16534. [Abstract] [Full Text] [PDF]

				K. J. Smith, G. Scotland, J. Beattie, I. P. Trayer, and M. D. Houslay 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., July 12, 1996; 271(28): 16703 - 16711. [Abstract] [Full Text] [PDF]

				M. Grange, C. Sette, M. Cuomo, M. Conti, M. Lagarde, A.-F. Prigent, and G. Nemoz 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., October 20, 2000; 275(43): 33379 - 33387. [Abstract] [Full Text] [PDF]

				I. Verde, G. Pahlke, M. Salanova, G. Zhang, S. Wang, D. Coletti, J. Onuffer, S.-L. C. Jin, and M. Conti Myomegalin Is a Novel Protein of the Golgi/Centrosome That Interacts with a Cyclic Nucleotide Phosphodiesterase J. Biol. Chem., March 30, 2001; 276(14): 11189 - 11198. [Abstract] [Full Text] [PDF]

				E. Huston, M. Beard, F. McCallum, N. J. Pyne, P. Vandenabeele, G. Scotland, and M. D. Houslay The cAMP-specific Phosphodiesterase PDE4A5 Is Cleaved Downstream of Its SH3 Interaction Domain by Caspase-3. CONSEQUENCES FOR ALTERED INTRACELLULAR DISTRIBUTION J. Biol. Chem., September 1, 2000; 275(36): 28063 - 28074. [Abstract] [Full Text] [PDF]

				T. C. Rich, K. A. Fagan, T. E. Tse, J. Schaack, D. M. F. Cooper, and J. W. Karpen A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell PNAS, November 6, 2001; 98(23): 13049 - 13054. [Abstract] [Full Text] [PDF]