Cyclic AMP, Protein Kinase A, and Phosphodiesterases: Proceedings of an International Workshop

C. A. Stratakis

doi:10.1055/s-0031-1301327

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2012; 44(10): 713-715
DOI: 10.1055/s-0031-1301327

Editorial

Cyclic AMP, Protein Kinase A, and Phosphodiesterases: Proceedings of an International Workshop

C. A. Stratakis

¹Section of Endocrinology and Genetics, Program on Developmental Endocrinology Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

› Author Affiliations

Abstract

Cyclic nucleotides cAMP and cGMP are part of almost all major cellular signaling pathways. Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cAMP and cGMP. Protein kinase A or cAMP-dependent protein kinase mediates most cAMP effects in the cell. Over the last 25 years, various components of this group of molecules have been involved in human diseases, both genetic and acquired. Lately, the PDEs attract more attention. The pharmacological exploitation of the PDE’s ability to regulate cGMP and cAMP, and through them, a variety of signaling pathways, has led to a number of new drugs for diverse applications from the treatment of erectile dysfunction to heart failure, asthma, and chronic obstructive pulmonary disease. We present the abstracts (available online) and selected articles from the proceedings of a meeting that took place at the National Institutes of Health (NIH), Bethesda, MD, June 8–10, 2011.

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References

References
1 Savai R, Pullamsetti SS, Banat GA, Weissmann N, Ghofrani HA, Grimminger F, Schermuly RT. Targeting cancer with phosphodiesterase inhibitors. Expert Opin Investig Drugs 2010; 19: 117-131
2 Makhlouf A, Kshirsagar A, Niederberger C. Phosphodiesterase 11: a brief review of structure, expression and function. Int J Impot Res 2006; 18: 501-509
3 Taskén K, Skålhegg BS, Taskén KA, Solberg R, Knutsen HK, Levy FO, Sandberg M, Orstavik S, Larsen T, Johansen AK, Vang T, Schrader HP, Reinton NT, Torgersen KM, Hansson V, Jahnsen T. Structure, function, and regulation of human cAMP-dependent protein kinases. Adv Second Messenger Phosphoprotein Res 1997; 31: 191-204
4 Kim C, Xuong NH, Taylor SS. Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA. Science 2005; 307 (5710) 690-696
5 Kim C, Cheng CY, Saldanha SA, Taylor SS. PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation. Cell 2007; 130: 1032-1043
6 Francis SH, Corbin JD. Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action. Crit Rev Clin Lab Sci 1999; 36: 275-328
7 Kim MJ, Lee JH, Park SY, Hong KW, Kim CD, Kim KY, Lee WS. Protection from apoptotic cell death by cilostazol, phosphodiesterase type III inhibitor, via cAMP-dependent protein kinase activation. Pharmacol Res 2006; 54: 261-267
8 Zhang L, Murray F, Zahno A, Kanter JR, Chou D, Suda R, Fenlon M, Rassenti L, Cottam H, Kipps TJ, Insel PA. Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2008; 105: 19532-19537
9 Sengupta R, Sun T, Warrington NM, Rubin JB. Treating brain tumors with PDE4 inhibitors. Trends Pharmacol Sci 2011; 32: 337-344
10 Jeon YH, Heo YS, Kim CM, Hyun YL, Lee TG, Ro S, Cho JM. Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell Mol Life Sci 2005; 62: 1198-1220
11 Bender AT, Beavo JA. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 2006; 58: 488-520
12 Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991; 325: 1688-1695
13 Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, Cho-Chung YS, Stratakis CA. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000; 26: 89-92
14 Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985; 64: 270-283
15 Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, Libé R, Rene-Corail F, Stergiopoulos S, Bourdeau I, Bei T, Clauser E, Calender A, Kirschner LS, Bertagna X, Carney JA, Stratakis CA. Mutations in regulatory subunit type 1 A of cyclic adenosine 5-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab 2009; 94: 2085-2091
16 Greene EL, Horvath AD, Nesterova M, Giatzakis C, Bossis I, Stratakis CA. In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Hum Mutat 2008; 29: 633-639
17 Groussin L, Kirschner LS, Vincent-Dejean C, Perlemoine K, Jullian E, Delemer B, Zacharieva S, Pignatelli D, Carney JA, Luton JP, Bertagna X, Stratakis CA, Bertherat J. Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1 A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD. Am J Hum Genet 2002; 71: 1433-1442
18 Horvath A, Bertherat J, Groussin L, Guillaud-Bataille M, Tsang K, Cazabat L, Libé R, Remmers E, Rene-Corail F, Faucz FR, Clauser E, Calender A, Bertagna X, Carney JA, Stratakis CA. Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Hum Mutat 2010; 31: 369-379
19 Rothenbuhler A, Stratakis CA. Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metab 2010; 24: 389-399
20 Bertherat J, Groussin L, Sandrini F, Matyakhina L, Bei T, Stergiopoulos S, Papageorgiou T, Bourdeau I, Kirschner LS, Vincent-Dejean C, Perlemoine K, Gicquel C, Bertagna X, Stratakis CA. Molecular and functional analysis of PRKAR1A and its locus (17q22–24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity. Cancer Res 2003; 63: 5308-5319
21 Horvath A, Boikos S, Giatzakis C, Robinson-White A, Groussin L, Griffin KJ, Stein E, Levine E, Delimpasi G, Hsiao HP, Keil M, Heyerdhal S, Matyakhina L, Libé R, Fratticci A, Kirschner LS, Craner K, Gaillard RC, Bertagna X, Carney JA, Bertherat J, Bossis I, Stratakis CA. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 2006; 38: 794-800
22 Horvath A, Giatzakis C, Robinson-White A, Boikos S, Levine E, Griffin K, Stein E, Kamvissi V, Soni P, Bossis I, De Herder W, Carney JA, Bertherat J, Gregersen PK, Remmers EF, Stratakis CA. Adrenal hyperplasia and adenomas are associated with inhibition of phosphodiesterase 11A in carriers of PDE11A sequence variants that are frequent in the population. Cancer Res 2006; 66: 11571-11575
23 Libé R, Fratticci A, Coste J, Tissier F, Horvath A, Ragazzon B, Rene-Corail F, Groussin L, Bertagna X, Raffin-Sanson ML, Stratakis CA, Bertherat J. Phosphodiesterase 11A (PDE11A) and genetic predisposition to adrenocortical tumors. Clin Cancer Res 2008; 14: 4016-4024
24 Libé R, Horvath A, Vezzosi D, Fratticci A, Coste J, Perlemoine K, Ragazzon B, Guillaud-Bataille M, Groussin L, Clauser E, Raffin-Sanson ML, Siegel J, Moran J, Drori-Herishanu L, Faucz FR, Lodish M, Nesterova M, Bertagna X, Bertherat J, Stratakis CA. Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype. J Clin Endocrinol Metab 2011; 96: E208-E214
25 Faucz FR, Horvath A, Rothenbuhler A, Almeida MQ, Libé R, Raffin-Sanson ML, Bertherat J, Carraro DM, Soares FA, GdeC Molina, Canpos AH, Alexandre RB, Bendhak ML, Nesterova M, Stratakis CA. Phosphodiesterase 11A (PDE11A) genetic variants may increase susceptibility to prostatic cancer. J Clin Endocrinol Metab 2011; 96: E135-E140
26 Horvath A, Giatzakis C, Tsang K, Greene E, Osorio P, Boikos S, Libé R, Patronas Y, Robinson-White A, Remmers E, Bertherat J, Nestrova M, Stratakis CA. A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex. Eur J Hum Genet 2008; 16: 1245-1253
27 Tsai LC, Shimizu-Albergine M, Beavo JA. The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal gland. Mol Pharmacol 2011; 79: 639-648
28 Horvath A, Mericq V, Stratakis CA. Mutation in PDE8B, a cyclic AMP-specific phosphodiesterase in adrenal hyperplasia. N Engl J Med 2008; 358: 750-752
29 Rothenbuhler A, Horvath A, Faucz F, Almeida M, Lodish M, Libé R, Nesterova M, Bertherat J, Stratakis CA. Three novel mutations in PDE8B, a cAMP phosphodiesterase highly expressed in the adrenal cortex, in a cohort of patients with adrenal tumors. Program of the 91st Annual Meeting of the Endocrine Society, Washington, DC 2009;
30 Bimpaki EI, Nesterova M, Stratakis CA. Abnormalities of cAMP signaling are present in adrenocortical lesions associated with ACTH-independent Cushing syndrome despite the absence of mutations in known genes. Eur J Endocrinol 2009; 161: 153-161
31 Hayashi M, Matsushima K, Ohashi H, Tsunoda H, Murase S, Kawarada Y, Tanaka T. Molecular cloning and characterization of human PDE8B, a novel thyroid-specific isozyme of 3′,5′-cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun 1998; 250: 751-756
32 Arnaud-Lopez L, Usala G, Ceresini G, Mitchell BD, Pilia MG, Piras MG, Sestu N, Maschio A, Busonero F, Albai G, Dei M, Lai S, Mulas A, Crisponi L, Tanaka T, Bandinelli S, Guralnik JM, Loi A, Balaci L, Sole G, Prinzis A, Mariotti S, Shuldiner AR, Cao A, Schlessinger D, Uda M, Abecasis GR, Nagaraja R, Sanna S, Naitza S. Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function. Am J Hum Genet 2008; 82: 1270-1280
33 Volpato CB, De Grandi A, Gögele M, Taliun D, Fuchsberger C, Facheris MF, Minelli C, Pattaro C, Pramstaller PP, Hicks AA. Linkage and association analysis of hyperthyrotropinaemia in an Alpine population reveal two novel loci on chromosomes 3q28–29 and 6q26–27. J Med Genet 2011; 48: 549-556
34 Lania A, Persani L, Ballaré E, Mantovani S, Losa M, Spada A. Constitutively active Gs alpha is associated with an increased phosphodiesterase activity in human growth hormone-secreting adenomas. J Clin Endocrinol Metab 1998; 83: 1624-1628
35 Knight WE, Yan C. Cardiac cyclic nucleotide phosphodiesterase: function, regulation, and therapeutic prospects. Horm Metab Res 2012; 44: 766-775
36 Mantovani G, Elli FM, Spada A. GNAS epigenetic defects and pseudohypoparathyroidism: time for a new classification?. Horm Metab Res 2012; 44: 716-723
37 Zhang S, Kaplan FS, Shore EM. Different roles of GNAS and cAMP signaling during early and late stages of osteogenic differentiation. Horm Metab Res 2012; 44: 724-731
38 Silve C, Clauser E, Linglart A. Acrodysostosis. Horm Metab Res 2012; 44: 749-758
39 Yu B, Ragazzon B, Rizk-Rabin M, Bertherat J. Protein kinase A alterations in endocrine tumors. Horm Metab Res 2012; 44: 741-748
40 Tsai LC, Beavo JA. Regulation of adrenal steroidogenesis by the high-affinity phosphodiesterase 8 family. Horm Metab Res 2012; 44: 790-794
41 Bastepe M. Relative functions of Gαs and its extra-large variant XLαs in the endocrine system. Horm Metab Res 2012; 44: 732-740
42 Ahmad F, Degerman E, Manganiello VC. Cyclic nucleotide phosphodiesterase 3 signaling complexes. Horm Metab Res 2012; 44: 776-785
43 Hussain MA, Stratakis CA, Kirschner L. Prkar1a in the regulation of insulin secretion. Horm Metab Res 2012; 44: 759-765
44 Vincent P, Castro LR, Gervasi N, Guiot E, Brito M, Paupardin-Tritsch D. PDE4 control on cAMP/PKA compartmentation revealed by biosensor imaging in neurons. Horm Metab Res 2012; 44: 786-789