Protein-Protein Interactions of Phosphodiesterases

Author(s): Mayasah Y. Al-Nema, Anand Gaurav*

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 7 , 2019

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Graphical Abstract:


Background: Phosphodiesterases (PDEs) are enzymes that play a key role in terminating cyclic nucleotides signalling by catalysing the hydrolysis of 3’, 5’- cyclic adenosine monophosphate (cAMP) and/or 3’, 5’ cyclic guanosine monophosphate (cGMP), the second messengers within the cell that transport the signals produced by extracellular signalling molecules which are unable to get into the cells. However, PDEs are proteins which do not operate alone but in complexes that made up of a many proteins.

Objective: This review highlights some of the general characteristics of PDEs and focuses mainly on the Protein-Protein Interactions (PPIs) of selected PDE enzymes. The objective is to review the role of PPIs in the specific mechanism for activation and thereby regulation of certain biological functions of PDEs.

Methods: The article discusses some of the PPIs of selected PDEs as reported in recent scientific literature. These interactions are critical for understanding the biological role of the target PDE.

Results: The PPIs have shown that each PDE has a specific mechanism for activation and thereby regulation a certain biological function.

Conclusion: Targeting of PDEs to specific regions of the cell is based on the interaction with other proteins where each PDE enzyme binds with specific protein(s) via PPIs.

Keywords: Phosphodiesterases, 3', 5' cyclic adenosine monophosphate, 3', 5' cyclic guanosine monophosphate, proteins, complexes, protein-protein interactions.

Suter, B.; Kittanakom, S.; Stagljar, I. Two-hybrid technologies in proteomics research. Curr. Opin. Biotechnol., 2008, 19(4), 316-323. [ 10.1016/j.copbio.2008.06.005]. [PMID: 18619540].
Wells, J.A. Systematic mutational analyses of protein-protein interfaces. Methods Enzymol., 1991, 202, 390-411. [ 10.1016/0076-6879(91)02020-A]. [PMID: 1723781].
Perrakis, A.; Romier, C. Assembly of protein complexes by coexpression in prokaryotic and eukaryotic hosts: An overview. Methods Mol. Biol., 2008, 426, 247-256. [ 10.1007/978-1-60327-058-8_15]. [PMID: 18542868].
Bernstein, F.C.; Koetzle, T.F.; Williams, G.J.; Meyer, E.F., Jr; Brice, M.D.; Rodgers, J.R.; Kennard, O.; Shimanouchi, T.; Tasumi, M. The Protein Data Bank: A computer-based archival file for macromolecular structures. J. Mol. Biol., 1977, 112(3), 535-542. [ 10.1016/S0022-2836(77)80200-3]. [PMID: 875032].
Braun, P.; Gingras, A.C. History of protein-protein interactions: From egg-white to complex networks. Proteomics, 2012, 12(10), 1478-1498. [ 10.1002/pmic.201100563]. [PMID: 22711592].
Yanagida, M. Functional proteomics; current achievements. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2002, 771(1-2), 89-106. [ 10.1016/S1570-0232(02)00074-0]. [PMID: 12015994].
Berggård, T.; Linse, S.; James, P. Methods for the detection and analysis of protein-protein interactions. Proteomics, 2007, 7(16), 2833-2842. [ 10.1002/pmic.200700131]. [PMID: 17640003].
Keskin, O.; Tuncbag, N.; Gursoy, A. Predicting protein–protein interactions from the molecular to the proteome level. Chem. Rev., 2016, 116(8), 4884-4909. [ 10.1021/acs.chemrev. 5b00683]. [PMID: 27074302].
Mackay, J.P.; Sunde, M.; Lowry, J.A.; Crossley, M.; Matthews, J.M. Protein interactions: is seeing believing? Trends Biochem. Sci., 2007, 32(12), 530-531. [ 10.1016/j.tibs.2007. 09.006]. [PMID: 17980603].
Chatr-Aryamontri, A.; Ceol, A.; Licata, L.; Cesareni, G. Protein interactions: Integration leads to belief. Trends Biochem. Sci., 2008, 33(6), 241-242. [ 10.1016/j.tibs.2008. 04.002]. [PMID: 18472267].
De Las Rivas, J.; Fontanillo, C. Protein-protein interactions essentials: Key concepts to building and analyzing interactome networks. PLOS Comput. Biol., 2010, 6(6), e1000807. [ 10.1371/journal.pcbi.1000807]. [PMID: 20589078].
Ma, B.; Elkayam, T.; Wolfson, H.; Nussinov, R. Protein-protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces. Proc. Natl. Acad. Sci. USA, 2003, 100(10), 5772-5777. [ 10.1073/ pnas.1030237100]. [PMID: 12730379].
Bogan, A.A.; Thorn, K.S. Anatomy of hot spots in protein interfaces. J. Mol. Biol., 1998, 280(1), 1-9. [ 10.1006/ jmbi.1998.1843]. [PMID: 9653027].
Chakrabarti, P.; Janin, J. Dissecting protein-protein recognition sites. Proteins, 2002, 47(3), 334-343. [ 10.1002/prot.10085]. [PMID: 11948787].
Guharoy, M.; Chakrabarti, P. Conservation and relative importance of residues across protein-protein interfaces. Proc. Natl. Acad. Sci. USA, 2005, 102(43), 15447-15452. [ 10.1073/ pnas.0505425102]. [PMID: 16221766].
Jones, S.; Thornton, J.M. Analysis of protein-protein interaction sites using surface patches. J. Mol. Biol., 1997, 272(1), 121-132. [ 10.1006/jmbi.1997.1234]. [PMID: 9299342].
Plach, M.G.; Semmelmann, F.; Busch, F.; Busch, M.; Heizinger, L.; Wysocki, V.H.; Merkl, R.; Sterner, R. Evolutionary diversification of protein-protein interactions by interface add-ons. Proc. Natl. Acad. Sci. USA, 2017, 114(40), E8333-E8342. [ 10.1073/pnas.1707335114]. [PMID: 28923934].
DeLano, W.L. Unraveling hot spots in binding interfaces: Progress and challenges. Curr. Opin. Struct. Biol., 2002, 12(1), 14-20. [ 10.1016/S0959-440X(02)00283-X]. [PMID: 11839484].
Apweiler, R.; Bairoch, A.; Wu, C.H.; Barker, W.C.; Boeckmann, B.; Ferro, S.; Gasteiger, E.; Huang, H.; Lopez, R.; Magrane, M.; Martin, M.J.; Natale, D.A.; O’Donovan, C.; Redaschi, N.; Yeh, L.S. UniProt: The universal protein knowledgebase. Nucleic Acids Res., 2004, 32(Database issue), D115-D119. [ 10.1093/nar/gkh131]. [PMID: 14681372].
Jones, S.; Thornton, J.M. Principles of protein-protein interactions. Proc. Natl. Acad. Sci. USA, 1996, 93(1), 13-20. [ 10.1073/pnas.93.1.13]. [PMID: 8552589].
Nooren, I.M.; Thornton, J.M. Diversity of protein-protein interactions. EMBO J., 2003, 22(14), 3486-3492. [ 10.1093/emboj/cdg359]. [PMID: 12853464].
Arnold, H.; Pette, D. Binding of aldolase and triosephosphate dehydrogenase to F-actin and modification of catalytic properties of aldolase. Eur. J. Biochem., 1970, 15(2), 360-366. [ 10.1111/j.1432-1033.1970.tb01016.x]. [PMID: 5502667].
Rao, V.S.; Srinivas, K.; Sujini, G.N.; Kumar, G.N. Protein-protein interaction detection: methods and analysis. Int. J. Proteomics, 2014, 2014147648. [ 10.1155/2014/147648]. [PMID: 24693427].
Li, Y.W.; Seager, M.A.; Wojcik, T.; Heman, K.; Molski, T.F.; Fernandes, A.; Langdon, S.; Pendri, A.; Gerritz, S.; Tian, Y.; Hong, Y.; Gallagher, L.; Merritt, J.R.; Zhang, C.; Westphal, R.; Zaczek, R.; Macor, J.E.; Bronson, J.J.; Lodge, N.J. Biochemical and behavioral effects of PDE10A inhibitors: Relationship to target site occupancy. Neuropharmacology, 2016, 102, 121-135. [ 10.1016/j.neuropharm.2015.10.037]. [PMID: 26522433].
Ahmad, F.; Murata, T.; Shimizu, K.; Degerman, E.; Maurice, D.; Manganiello, V. Cyclic nucleotide phosphodiesterases: Important signaling modulators and therapeutic targets. Oral Dis., 2015, 21(1), e25-e50. [ 10.1111/odi.12275]. [PMID: 25056711].
Ejiofor, S.; Turner, A.M. Pharmacotherapies for COPD. Clin. Med. Insights Circ. Respir. Pulm. Med., 2013, 7, 17-34. [ 10.4137/CCRPM.S7211]. [PMID: 23700381].
Eschenhagen, T. PDE4 in the human heart - major player or little helper? Br. J. Pharmacol., 2013, 169(3), 524-527. [ 10.1111/bph.12168]. [PMID: 23489196].
Brand, T.; Klussmann, E. Cyclic Nucleotide Signaling and the Cardiovascular System., 2018.
Azevedo, M.F.; Faucz, F.R.; Bimpaki, E.; Horvath, A.; Levy, I.; de Alexandre, R.B.; Ahmad, F.; Manganiello, V.; Stratakis, C.A. Clinical and molecular genetics of the phosphodiesterases (PDEs). Endocr. Rev., 2014, 35(2), 195-233. [ 10.1210/er. 2013-1053]. [PMID: 24311737].
Maurice, D.H.; Ke, H.; Ahmad, F.; Wang, Y.; Chung, J.; Manganiello, V.C. Advances in targeting cyclic nucleotide phosphodiesterases. Nat. Rev. Drug Discov., 2014, 13(4), 290-314. [ 10.1038/nrd4228]. [PMID: 24687066].
Omori, K.; Kotera, J. Overview of PDEs and their regulation. Circ. Res., 2007, 100(3), 309-327. [ 10.1161/01. RES.0000256354.95791.f1]. [PMID: 17307970].
Bender, A.T.; Beavo, J.A. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol. Rev., 2006, 58(3), 488-520. [ 10.1124/pr.58.3.5]. [PMID: 16968949].
Goraya, T.A.; Cooper, D.M. Ca2+-calmodulin-dependent phosphodiesterase (PDE1): Current perspectives. Cell. Signal., 2005, 17(7), 789-797. [ 10.1016/j.cellsig.2004.12.017]. [PMID: 15763421].
Yan, C.; Zhao, A.Z.; Bentley, J.K.; Beavo, J.A. The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner. J. Biol. Chem., 1996, 271(41), 25699-25706. [ 10.1074/jbc.271.41.25699]. [PMID: 8810348].
Miller, C.L.; Oikawa, M.; Cai, Y.; Wojtovich, A.P.; Nagel, D.J.; Xu, X.; Xu, H.; Florio, V.; Rybalkin, S.D.; Beavo, J.A.; Chen, Y.F.; Li, J.D.; Blaxall, B.C.; Abe, J.; Yan, C. Role of Ca2+/calmodulin-stimulated cyclic nucleotide phosphodiesterase 1 in mediating cardiomyocyte hypertrophy. Circ. Res., 2009, 105(10), 956-964. [ 10.1161/CIRCRESAHA. 109.198515]. [PMID: 19797176].
Nagel, D.J.; Aizawa, T.; Jeon, K.I.; Liu, W.; Mohan, A.; Wei, H.; Miano, J.M.; Florio, V.A.; Gao, P.; Korshunov, V.A.; Berk, B.C.; Yan, C. Role of nuclear Ca2+/calmodulin-stimulated phosphodiesterase 1A in vascular smooth muscle cell growth and survival. Circ. Res., 2006, 98(6), 777-784. [ 10.1161/01. RES.0000215576.27615.fd]. [PMID: 16514069].
Shafiee-Nick, R.; Afshari, A.R.; Mousavi, S.H.; Rafighdoust, A.; Askari, V.R.; Mollazadeh, H.; Fanoudi, S.; Mohtashami, E.; Rahimi, V.B.; Mohebbi, M.; Vahedi, M.M. A comprehensive review on the potential therapeutic benefits of phosphodiesterase inhibitors on cardiovascular diseases. Biomed. Pharmacother., 2017, 94, 541-556. [ 10.1016/j.biopha.2017.07.084]. [PMID: 28779712].
Francis, S.H.; Blount, M.A.; Corbin, J.D. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol. Rev., 2011, 91(2), 651-690. [ 10.1152/physrev.00030.2010]. [PMID: 21527734].
Sorensen, A.B.; Søndergaard, M.T.; Overgaard, M.T. Calmodulin in a heartbeat. FEBS J., 2013, 280(21), 5511-5532. [ 10.1111/febs.12337]. [PMID: 23663249].
Kawaguchi, S.Y.; Hirano, T. Gating of long-term depression by Ca2+/calmodulin-dependent protein kinase II through enhanced cGMP signalling in cerebellar Purkinje cells. J. Physiol., 2013, 591(7), 1707-1730. [ 10.1113/jphysiol.2012. 245787]. [PMID: 23297306].
Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific therapeutic agents. Pharmacol. Ther., 2006, 109(3), 366-398. [ 10.1016/j.pharmthera.2005.07.003]. [PMID: 16102838].
Jeon, Y.H.; Heo, Y.S.; Kim, C.M.; Hyun, Y.L.; Lee, T.G.; Ro, S.; Cho, J.M. Phosphodiesterase: Overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell. Mol. Life Sci., 2005, 62(11), 1198-1220. [ 10.1007/s00018-005-4533-5]. [PMID: 15798894].
Movsesian, M.; Ahmad, F.; Hirsch, E. Functions of PDE3 isoforms in cardiac muscle. J. Cardiovasc. Dev. Dis., 2018, 5(1), 5. [ 10.3390/jcdd5010010]. [PMID: 29415428].
Degerman, E.; Belfrage, P.; Manganiello, V.C. Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). J. Biol. Chem., 1997, 272(11), 6823-6826. [ 10.1074/jbc.272.11.6823]. [PMID: 9102399].
Elbatarny, H.S.; Maurice, D.H. Leptin-mediated activation of human platelets: Involvement of a leptin receptor and phosphodiesterase 3A-containing cellular signaling complex. Am. J. Physiol. Endocrinol. Metab., 2005, 289(4), E695-E702. [ 10.1152/ajpendo.00125.2005]. [PMID: 15886225].
Palmer, D.; Jimmo, S.L.; Raymond, D.R.; Wilson, L.S.; Carter, R.L.; Maurice, D.H. Protein kinase A phosphorylation of human phosphodiesterase 3B promotes 14-3-3 protein binding and inhibits phosphatase-catalyzed inactivation. J. Biol. Chem., 2007, 282(13), 9411-9419. [ 10.1074/jbc.M606936200]. [PMID: 17255105].
Degerman, E.; Smith, C.J.; Tornqvist, H.; Vasta, V.; Belfrage, P.; Manganiello, V.C. Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation. Proc. Natl. Acad. Sci. USA, 1990, 87(2), 533-537. [ 10.1073/pnas.87.2.533]. [PMID: 2153956].
Ahmad, F.; Cong, L-N.; Stenson Holst, L.; Wang, L-M.; Rahn Landstrom, T.; Pierce, J.H.; Quon, M.J.; Degerman, E.; Manganiello, V.C. 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., 2000, 164(9), 4678-4688. [ 10.4049/jimmunol.164.9.4678]. [PMID: 10779773].
Ahmad, F.; Lindh, R.; Tang, Y.; Weston, M.; Degerman, E.; Manganiello, V.C. Insulin-induced formation of macromolecular complexes involved in activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and its interaction with PKB. Biochem. J., 2007, 404(2), 257-268. [ 10.1042/BJ20060960]. [PMID: 17324123].
Nilsson, R.; Ahmad, F.; Swärd, K.; Andersson, U.; Weston, M.; Manganiello, V.; Degerman, E. Plasma membrane cyclic nucleotide phosphodiesterase 3B (PDE3B) is associated with caveolae in primary adipocytes. Cell. Signal., 2006, 18(10), 1713-1721. [ 10.1016/j.cellsig.2006.01.010]. [PMID: 16503395].
Patrucco, E.; Notte, A.; Barberis, L.; Selvetella, G.; Maffei, A.; Brancaccio, M.; Marengo, S.; Russo, G.; Azzolino, O.; Rybalkin, S.D.; Silengo, L.; Altruda, F.; Wetzker, R.; Wymann, M.P.; Lembo, G.; Hirsch, E. PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell, 2004, 118(3), 375-387. [ 10.1016/j.cell.2004.07.017]. [PMID: 15294162].
Voigt, P.; Dorner, M.B.; Schaefer, M. Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B. J. Biol. Chem., 2006, 281(15), 9977-9986. [ 10.1074/jbc.M512502200]. [PMID: 16476736].
Wilson, L.S.; Baillie, G.S.; Pritchard, L.M.; Umana, B.; Terrin, A.; Zaccolo, M.; Houslay, M.D.; Maurice, D.H. A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. J. Biol. Chem., 2011, 286(18), 16285-16296. [ 10.1074/jbc.M110.217026]. [PMID: 21393242].
Mongillo, M.; McSorley, T.; Evellin, S.; Sood, A.; Lissandron, V.; Terrin, A.; Huston, E.; Hannawacker, A.; Lohse, M.J.; Pozzan, T.; Houslay, M.D.; Zaccolo, M. Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases. Circ. Res., 2004, 95(1), 67-75. [ 10.1161/01.RES.0000134629.84732.11]. [PMID: 15178638].
Francis, S.H.; Conti, M.; Houslay, M.D. Phosphodiesterases as drug targets, 1st ed; Springer-Verlag Berlin Heidelberg, 2011. [ 10.1007/978-3-642-17969-3]
Houslay, M.D. Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem. Sci., 2010, 35(2), 91-100. [ 10.1016/j.tibs.2009.09.007]. [PMID: 19864144].
Houslay, M.D.; Baillie, G.S.; Maurice, D.H. cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: A molecular toolbox for generating compartmentalized cAMP signaling. Circ. Res., 2007, 100(7), 950-966. [ 10.1161/01.RES.0000261934.56938.38]. [PMID: 17431197].
Huston, E.; Lynch, M.J.; Mohamed, A.; Collins, D.M.; Hill, E.V.; MacLeod, R.; Krause, E.; Baillie, G.S.; Houslay, M.D. EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation. Proc. Natl. Acad. Sci. USA, 2008, 105(35), 12791-12796. [ 10.1073/pnas.0805167105]. [PMID: 18728186].
Mongillo, M.; Tocchetti, C.G.; Terrin, A.; Lissandron, V.; Cheung, Y.F.; Dostmann, W.R.; Pozzan, T.; Kass, D.A.; Paolocci, N.; Houslay, M.D.; Zaccolo, M. Compartmentalized phosphodiesterase-2 activity blunts beta-adrenergic cardiac inotropy via an NO/cGMP-dependent pathway. Circ. Res., 2006, 98(2), 226-234. [ 10.1161/01.RES.0000200178.34179.93]. [PMID: 16357307].
Szaszák, M.; Christian, F.; Rosenthal, W.; Klussmann, E. Compartmentalized cAMP signalling in regulated exocytic processes in non-neuronal cells. Cell. Signal., 2008, 20(4), 590-601. [ 10.1016/j.cellsig.2007.10.020]. [PMID: 18061403].
Dodge, K.L.; Khouangsathiene, S.; Kapiloff, M.S.; Mouton, R.; Hill, E.V.; Houslay, M.D.; Langeberg, L.K.; Scott, J.D. mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J., 2001, 20(8), 1921-1930. [ 10.1093/emboj/20.8.1921]. [PMID: 11296225].
Passariello, C.L.; Li, J.; Dodge-Kafka, K.; Kapiloff, M.S. mAKAP-a master scaffold for cardiac remodeling. J. Cardiovasc. Pharmacol., 2015, 65(3), 218-225. [ 10.1097/ FJC.0000000000000206]. [PMID: 25551320].
Sette, C.; Conti, M. 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., 1996, 271(28), 16526-16534. [ 10.1074/jbc.271. 28.16526]. [PMID: 8663227].
Carlisle Michel, J.J.; Dodge, K.L.; Wong, W.; Mayer, N.C.; Langeberg, L.K.; Scott, J.D. PKA-phosphorylation of PDE4D3 facilitates recruitment of the mAKAP signalling complex. Biochem. J., 2004, 381(Pt 3), 587-592. [ 10.1042/BJ200 40846]. [PMID: 15182229].
Klussmann, E. Protein-protein interactions of PDE4 family members - Functions, interactions and therapeutic value. Cell. Signal., 2016, 28(7), 713-718. [ 10.1016/j.cellsig. 2015.10.005]. [PMID: 26498857].
Torres-Quesada, O.; Mayrhofer, J.E.; Stefan, E. The many faces of compartmentalized PKA signalosomes. Cell. Signal., 2017, 37, 1-11. [ 10.1016/j.cellsig.2017.05.012]. [PMID: 28528970].
Taskén, K.A.; Collas, P.; Kemmner, W.A.; Witczak, O.; Conti, M.; Taskén, K. Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in the centrosomal area. J. Biol. Chem., 2001, 276(25), 21999-22002. [ 10.1074/jbc.C000911200]. [PMID: 11285255].
Loughney, K.; Hill, T.R.; Florio, V.A.; Uher, L.; Rosman, G.J.; Wolda, S.L.; Jones, B.A.; Howard, M.L.; McAllister-Lucas, L.M.; Sonnenburg, W.K.; Francis, S.H.; Corbin, J.D.; Beavo, J.A.; Ferguson, K. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesterase. Gene, 1998, 216(1), 139-147. [ 10.1016/S0378-1119(98)00303-5]. [PMID: 9714779].
McAllister-Lucas, L.M.; Haik, T.L.; Colbran, J.L.; Sonnenburg, W.K.; Seger, D.; Turko, I.V.; Beavo, J.A.; Francis, S.H.; Corbin, J.D. An essential aspartic acid at each of two allosteric cGMP-binding sites of a cGMP-specific phosphodiesterase. J. Biol. Chem., 1995, 270(51), 30671-30679. [ 10.1074/jbc.270.51.30671]. [PMID: 8530505].
Blount, M.A.; Zoraghi, R.; Ke, H.; Bessay, E.P.; Corbin, J.D.; Francis, S.H. A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization. Mol. Pharmacol., 2006, 70(5), 1822-1831. [ 10.1124/mol.106.028688]. [PMID: 16926278].
Francis, S.H.; Bessay, E.P.; Kotera, J.; Grimes, K.A.; Liu, L.; Thompson, W.J.; Corbin, J.D. Phosphorylation of isolated human phosphodiesterase-5 regulatory domain induces an apparent conformational change and increases cGMP binding affinity. J. Biol. Chem., 2002, 277(49), 47581-47587. [ 10.1074/jbc.M206088200]. [PMID: 12359732].
Rybalkin, S.D.; Rybalkina, I.G.; Shimizu-Albergine, M.; Tang, X.B.; Beavo, J.A. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. EMBO J., 2003, 22(3), 469-478. [ 10.1093/emboj/cdg051]. [PMID: 12554648].
Schlossmann, J.; Ammendola, A.; Ashman, K.; Zong, X.; Huber, A.; Neubauer, G.; Wang, G-X.; Allescher, H-D.; Korth, M.; Wilm, M.; Hofmann, F.; Ruth, P. Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature, 2000, 404(6774), 197-201. [ 10.1038/35004606]. [PMID: 10724174].
Antl, M.; von Brühl, M-L.; Eiglsperger, C.; Werner, M.; Konrad, I.; Kocher, T.; Wilm, M.; Hofmann, F.; Massberg, S.; Schlossmann, J. IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation. Blood, 2007, 109(2), 552-559. [ 10.1182/blood-2005-10-026294]. [PMID: 16990611].
Wilson, L.S.; Elbatarny, H.S.; Crawley, S.W.; Bennett, B.M.; Maurice, D.H. Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. Proc. Natl. Acad. Sci. USA, 2008, 105(36), 13650-13655. [ 10.1073/pnas.0804738105]. [PMID: 18757735].
Arshavsky, V.Y.; Burns, M.E. Photoreceptor signaling: supporting vision across a wide range of light intensities. J. Biol. Chem., 2012, 287(3), 1620-1626. [ 10.1074/jbc.R111.305243]. [PMID: 22074925].
Gao, X. Regulation of photoreceptor phosphodiesterase and its activation by transducin elucidated by structural and biochemical approaches; University of New Hmapshire: Durham, 2017.
Zhang, X.J.; Skiba, N.P.; Cote, R.H. Structural requirements of the photoreceptor phosphodiesterase gamma-subunit for inhibition of rod PDE6 holoenzyme and for its activation by transducin. J. Biol. Chem., 2010, 285(7), 4455-4463. [ 10.1074/jbc. M109.057406]. [PMID: 19948718].
Zhang, X.J.; Gao, X.Z.; Yao, W.; Cote, R.H. Functional mapping of interacting regions of the photoreceptor phosphodiesterase (PDE6) γ-subunit with PDE6 catalytic dimer, transducin, and regulator of G-protein signaling9-1 (RGS9-1). J. Biol. Chem., 2012, 287(31), 26312-26320. [ 10.1074/jbc. M112.377333]. [PMID: 22665478].
Guo, L.W.; Hajipour, A.R.; Ruoho, A.E. Complementary interactions of the rod PDE6 inhibitory subunit with the catalytic subunits and transducin. J. Biol. Chem., 2010, 285(20), 15209-15219. [ 10.1074/jbc.M109.086116]. [PMID: 20231289].
Yamazaki, A.; Hayashi, F.; Matsuura, I.; Bondarenko, V.A. Binding of cGMP to the transducin-activated cGMP phosphodiesterase, PDE6, initiates a large conformational change involved in its deactivation. FEBS J., 2011, 278(11), 1854-1872. [ 10.1111/j.1742-4658.2011.08104.x]. [PMID: 21439020].
Qureshi, B.M.; Behrmann, E.; Schöneberg, J.; Loerke, J.; Bürger, J.; Mielke, T.; Giesebrecht, J.; Noé, F.; Lamb, T.D.; Hofmann, K.P.; Spahn, C.M.T.; Heck, M. It takes two transducins to activate the cGMP-phosphodiesterase 6 in retinal rods. Open Biol., 2018, 8(8), 180075. [ 10.1098/rsob.180075]. [PMID: 30068566].
Das, R.; Esposito, V.; Abu-Abed, M.; Anand, G.S.; Taylor, S.S.; Melacini, G. cAMP activation of PKA defines an ancient signaling mechanism. Proc. Natl. Acad. Sci. USA, 2007, 104(1), 93-98. [ 10.1073/pnas.0609033103]. [PMID: 17182741].
Kim, C.; Xuong, N.H.; Taylor, S.S. Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA. Science, 2005, 307(5710), 690-696. [ 10.1126/ science.1104607]. [PMID: 15692043].
Taylor, S.S.; Zhang, P.; Steichen, J.M.; Keshwani, M.M.; Kornev, A.P. PKA: Lessons learned after twenty years. Biochim. Biophys. Acta, 2013, 1834(7), 1271-1278. [ 10.1016/ j.bbapap.2013.03.007]. [PMID: 23535202].
Huang, Y.M.; Huber, G.; McCammon, J.A. Electrostatic steering enhances the rate of cAMP binding to phosphodiesterase: Brownian dynamics modeling. Protein Sci., 2015, 24(11), 1884-1889. [ 10.1002/pro.2794]. [PMID: 26346301].
Tulsian, N.K.; Krishnamurthy, S.; Anand, G.S. Channeling of cAMP in PDE-PKA complexes promotes signal adaptation. Biophys. J., 2017, 112(12), 2552-2566. [ 10.1016/ j.bpj.2017.04.045]. [PMID: 28636912].
Shepherd, G.M. Corticostriatal connectivity and its role in disease. Nat. Rev. Neurosci., 2013, 14(4), 278-291. [ 10.1038/nrn3469]. [PMID: 23511908].
Hersch, S.M.; Ciliax, B.J.; Gutekunst, C.A.; Rees, H.D.; Heilman, C.J.; Yung, K.K.; Bolam, J.P.; Ince, E.; Yi, H.; Levey, A.I. Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents. J. Neurosci., 1995, 15(7 Pt 2), 5222-5237. []. [PMID: 7623147].
Bolam, J.P.; Hanley, J.J.; Booth, P.A.; Bevan, M.D. Synaptic organisation of the basal ganglia. J. Anat., 2000, 196(Pt 4), 527-542. [ 10.1046/j.1469-7580.2000.19640527.x]. [PMID: 10923985].
Fujishige, K.; Kotera, J.; Omori, K. Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A. Eur. J. Biochem., 1999, 266(3), 1118-1127. []. [PMID: 10583409].
Xie, Z.; Adamowicz, W.O.; Eldred, W.D.; Jakowski, A.B.; Kleiman, R.J.; Morton, D.G.; Stephenson, D.T.; Strick, C.A.; Williams, R.D.; Menniti, F.S. Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase. Neuroscience, 2006, 139(2), 597-607. [ 10.1016/j.neuroscience. 2005.12.042]. [PMID: 16483723].
Seeger, T.F.; Bartlett, B.; Coskran, T.M.; Culp, J.S.; James, L.C.; Krull, D.L.; Lanfear, J.; Ryan, A.M.; Schmidt, C.J.; Strick, C.A.; Varghese, A.H.; Williams, R.D.; Wylie, P.G.; Menniti, F.S. Immunohistochemical localization of PDE10A in the rat brain. Brain Res., 2003, 985(2), 113-126. [ 10.1016/S0006-8993(03)02754-9]. [PMID: 12967715].
Russwurm, C.; Koesling, D.; Russwurm, M. Phosphodiesterase 10A is tethered to a synaptic signaling complex in striatum. J. Biol. Chem., 2015, 290(19), 11936-11947. [ 10.1074/jbc.M114.595769]. [PMID: 25762721].

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Article Details

Year: 2019
Published on: 30 May, 2019
Page: [555 - 564]
Pages: 10
DOI: 10.2174/1568026619666190401113803
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