The Role of Cyclic AMP in Regulating the Androgen Receptor



The androgen receptor (AR) is suggested to play a predominant role in the recurrence of prostate cancer in patients receiving androgen ablation therapy. In the absence of androgens, the AR is activated by compounds that increase cyclic adenosine 3′,5′-monophosphate (cAMP) and stimulate cAMP-dependent protein kinase (PKA) activity in prostate cancer cells. Thus cross-talk between AR and cAMP/PKA pathways is suspected to be involved in the mechanism underlying castration-recurrent prostate cancer. Elucidation of the molecular mechanism(s) of how the AR can be activated by alternative pathways such as cAMP/PKA in the absence of androgen may yield new therapeutic targets for the improved clinical management of advanced prostate cancer.


Prostate Cancer Androgen Receptor Prostate Cancer Cell Adenylyl Cyclase LNCaP Cell 



I apologize to those authors whose work were inadvertently overlooked or could not be included due to limitations of space. Thank you to Dr. Joanne Johnson for helping prepare the manuscript. This work was supported by the National Institutes of Health CA105304 and the Canadian Institutes for Health Research MOP79308.


  1. Agrawal S, Kandimalla ER, Yu D, Ball R, Lombardi G, Lucas T, Dexter DL, Hollister BA, Chen SF (2002) GEM 231, a second-generation antisense agent complementary to protein kinase A RIalpha subunit, potentiates antitumor activity of irinotecan in human colon, pancreas, prostate and lung cancer xenografts. Int J Oncol 21:65–72.PubMedGoogle Scholar
  2. Ahn S, Olive M, Aggarwal S, Krylov D, Ginty DD, Vinson C (1998) A dominant-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos. Mol Cell Biol 18:967–977.PubMedGoogle Scholar
  3. Andrews PE, Young CY, Montgomery BT, Tindall DJ (1992) Tumor-promoting phorbol ester down-regulates the androgen induction of prostate-specific antigen in a human prostatic adenocarcinoma cell line. Cancer Res 52:1525–1529.PubMedGoogle Scholar
  4. Aprikian AG, Han K, Chevalier S, Bazinet M, Viallet J (1996) Bombesin specifically induces intracellular calcium mobilization via gastrin-releasing peptide receptors in human prostate cancer cells. J Mol Endocrinol 16:297–306.PubMedGoogle Scholar
  5. Bai W, Rowan BG, Allgood VE, O'Malley BW, Weigel NL (1997) Differential phosphorylation of chicken progesterone receptor in hormone-dependent and ligand-independent activation. J Biol Chem 272:10457–10463.PubMedGoogle Scholar
  6. Bang YJ, Pirnia F, Fang WGet al. (1994) Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. Proc Natl Acad Sci USA 91:5330–5334.PubMedGoogle Scholar
  7. Bartholdi MF, Wu JM, Pu H, Troncoso P, Eden PA, Feldman RI (1998) In situ hybridization for gastrin-releasing peptide receptor (GRP receptor) expression in prostatic carcinoma. Int J Cancer 79:82–90.PubMedGoogle Scholar
  8. Beavo JA (1995) Cyclic nucleotide phosphodiesterases: Functional implications of multiple isoforms. Physiol Rev 75:725–748.PubMedGoogle Scholar
  9. Black BE, Vitto MJ, Gioeli D, Spencer A, Afshar N, Conaway MR, Weber MJ, Paschal BM (2004) Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci alters phosphorylation and coactivator interactions. Mol Endocrinol 18:834–850.PubMedGoogle Scholar
  10. Blaszczyk N, Masri BA, Mawji NRet al. (2004) Osteoblast-derived factors induce androgen-independent proliferation and expression of prostate-specific antigen in human prostate cancer cells. Clin Cancer Res 10:1860–1869.PubMedGoogle Scholar
  11. Blok LJ, de Ruiter PE, Brinkmann AO (1998) Forskolin-induced dephosphorylation of the androgen receptor impairs ligand binding. Biochemistry 37:3850–3857.PubMedGoogle Scholar
  12. Bolger GB, McPhee I, Houslay MD (1996) Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts. Characterization of a novel tissue-specific isoform, RNPDE4A8. J Biol Chem 271:1065–1071.Google Scholar
  13. Bos JL (2003) EPAC: A new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4:733–738.PubMedGoogle Scholar
  14. Bos JL (2005) Linking rap to cell adhesion. Curr Opin Cell Biol 17:123–128.PubMedGoogle Scholar
  15. Bruchovsky N, Goldenberg SL, Mawji NR, Sadar MD. (2001) Evolving aspects of intermittent androgen blockage for prostate cancer: Diagnosis and treatment of early tumor progression and maintenance of remission. Andrology in the 21st Century, Proceedings of the VIIth International Congress of Andrology 609–623.Google Scholar
  16. Buchs N, Bonjour JP, Rizzoli R (1998) Renal tubular reabsorption of phosphate is positively related to the extent of bone metastatic load in patients with prostate cancer. J Clin Endocrinol Metab 83:1535–1541.PubMedGoogle Scholar
  17. Buck J, Sinclair ML, Schapal L, Cann MJ, Levin LR (1999) Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. Proc Natl Acad Sci USA 96:79–84.PubMedGoogle Scholar
  18. Burchardt T, Burchardt M, Chen MW, Cao Y, de la Taille A, Shabsigh A, Hayek O, Dorai T, Buttyan R (1999) Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo. J Urol 162:1800–1805.PubMedGoogle Scholar
  19. Cali JJ, Parekh RS, Krupinski J (1996) Splice variants of type VIII adenylyl cyclase: Differences in glycosylation and regulation by Ca2+/calmodulin. J Biol Chem 271:1089–1095.PubMedGoogle Scholar
  20. Carmena MJ, Prieto JC (1983) Cyclic AMP-stimulating effect of vasoactive intestinal peptide in isolated epithelial cells of rat ventral prostate. Biochim Biophys Acta 763:414–418.PubMedGoogle Scholar
  21. Carmena MJ, Hueso C, Recio MN, Prieto JC (1990) Beta-adrenergic stimulation of cyclic AMP accumulation in rat prostatic epithelial cells during sexual maturation. Mech Ageing Dev 52:79–86.PubMedGoogle Scholar
  22. Cao X, Qin J, Xie Y, Khan O, Dowd F, Scofield M, Lin MF, Tu Y (2006) Regulator of G-protein signaling 2 (RGS2) inhibits androgen-independent activation of androgen receptor in prostate cancer cells. Oncogene 25:3719–3734.PubMedGoogle Scholar
  23. Chaturvedi D, Poppleton HM, Stringfield T, Barbier A, Patel TB (2006) Subcellular localization and biological actions of activated RSK1 are determined by its interactions with subunits of cyclic AMP-dependent protein kinase. Mol Cell Biol 26:4586–4600.PubMedGoogle Scholar
  24. Chauchereau A, Amazit L, Quesne M, Guiochon-Mantel A, Milgrom E (2003) Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC-1. J Biol Chem 278:12335–12343.PubMedGoogle Scholar
  25. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10:33–39.PubMedGoogle Scholar
  26. Chen Y, Cann MJ, Litvin TN, Iourgenko V, Sinclair ML, Levin LR, Buck J (2000) Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289:625–628.PubMedGoogle Scholar
  27. Chien J, Shah GV (2001) Role of stimulatory guanine nucleotide binding protein (GSalpha) in proliferation of PC-3M prostate cancer cells. Int J Cancer 91:46–54.PubMedGoogle Scholar
  28. Cho YS, Cho-Chung YS (2003) Antisense protein kinase A RIalpha acts synergistically with hydroxycamptothecin to inhibit growth and induce apoptosis in human cancer cells: Molecular basis for combinatorial therapy. Clin Cancer Res 9:1171–1178.PubMedGoogle Scholar
  29. Cho YS, Lee YN, Cho-Chung YS (2000a) Biochemical characterization of extracellular cAMP-dependent protein kinase as a tumor marker. Biochem Biophys Res Commun 278:679–684.Google Scholar
  30. Cho YS, Park YG, Lee YN, Kim MK, Bates S, Tan L, Cho-Chung YS (2000b) Extracellular protein kinase A as a cancer biomarker: Its expression by tumor cells and reversal by a myristate-lacking calpha and RIIbeta subunit overexpression. Proc Natl Acad Sci USA 97:835–840.Google Scholar
  31. Cho-Chung YS, Nesterova MV (2005) Tumor reversion: Protein kinase A isozyme switching. Ann NY Acad Sci 1058:76–86.PubMedGoogle Scholar
  32. Choi EJ, Xia Z, Storm DR (1992) Stimulation of the type III olfactory adenylyl cyclase by calcium and calmodulin. Biochemistry 31:6492–6498.PubMedGoogle Scholar
  33. Christensen AE, Selheim F, de Rooij Jet al. (2003) cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that EPAC and cAMP kinase act synergistically to promote PC-12 cell neurite extension. J Biol Chem 278:35394–35402.PubMedGoogle Scholar
  34. Clark DE, Errington TM, Smith JA, Frierson HF, Jr, Weber MJ, Lannigan DA (2005) The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation. Cancer Res 65:3108–3116.PubMedGoogle Scholar
  35. Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J (1996) Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem 271:6379–6388.PubMedGoogle Scholar
  36. Cleutjens KB, van der Korput HA, van Eekelen CC, van Rooij HC, Faber PW, Trapman J (1997) An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter. Mol Endocrinol 11:148–161.PubMedGoogle Scholar
  37. Collins S, Quarmby VE, French FS, Lefkowitz RJ, Caron MG (1988) Regulation of the beta 2-adrenergic receptor and its mRNA in the rat ventral prostate by testosterone. FEBS Lett 233:173–176.PubMedGoogle Scholar
  38. Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, Montminy M (2003) TORCs: Transducers of regulated CREB activity. Mol Cell 12:413–423.PubMedGoogle Scholar
  39. Corbin JD, Sugden PH, West L, Flockhart DA, Lincoln TM, McCarthy D (1978) Studies on the properties and mode of action of the purified regulatory subunit of bovine heart adenosine 3′:5′-monophosphate-dependent protein kinase. J Biol Chem 253:3997–4003.PubMedGoogle Scholar
  40. Cox ME, Deeble PD, Lakhani S, Parsons SJ (1999) Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: Implications for prostate cancer progression. Cancer Res 59:3821–3830.PubMedGoogle Scholar
  41. Cox ME, Deeble PD, Bissonette EA, Parsons SJ (2000) Activated 3′???,5′-cyclic AMP-dependent protein kinase is sufficient to induce neuroendocrine-like differentiation of the LNCaP prostate tumor cell line. J Biol Chem 275:13812–13818.PubMedGoogle Scholar
  42. Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, Bartsch G, Klocker H (1994) Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54:5474–5478.PubMedGoogle Scholar
  43. Culig Z, Hobisch A, Hittmair A, Cronauer MV, Radmayr C, Zhang J, Bartsch G, Klocker H (1997) Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells. Prostate 32:106–114.PubMedGoogle Scholar
  44. Cvijic ME, Kita T, Shih W, DiPaola RS, Chin KV (2000) Extracellular catalytic subunit activity of the cAMP-dependent protein kinase in prostate cancer. Clin Cancer Res 6:2309–2317.PubMedGoogle Scholar
  45. Dai J, Shen R, Sumitomo M, Stahl R, Navarro D, Gershengorn MC, Nanus DM (2002) Synergistic activation of the androgen receptor by bombesin and low-dose androgen. Clin Cancer Res 8:2399–2405.PubMedGoogle Scholar
  46. D'Andrea MR, Qiu Y, Haynes-Johnson D, Bhattacharjee S, Kraft P, Lundeen S (2005) Expression of PDE11A in normal and malignant human tissues. J Histochem Cytochem 53:895–903.PubMedGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. Defer N, Best-Belpomme M, Hanoune J (2000) Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase. Am J Physiol Renal Physiol 279:F400–F416.PubMedGoogle Scholar
  49. Dehm SM, Tindall DJ (2006a) Ligand-independent androgen receptor activity is activation function-2-independent and resistant to antiandrogens in androgen refractory prostate cancer cells. J Biol Chem 281:27882–27893.Google Scholar
  50. Dehm SM, Tindall DJ (2006b) Molecular regulation of androgen action in prostate cancer. J Cell Biochem 99:333–344.Google Scholar
  51. Desdouets C, Matesic G, Molina CA, Foulkes NS, Sassone-Corsi P, Brechot C, Sobczak-Thepot J (1995) Cell cycle regulation of cyclin A gene expression by the cyclic AMP-responsive transcription factors CREB and CREM. Mol Cell Biol 15:3301–3309.PubMedGoogle Scholar
  52. Dotzlaw H, Moehren U, Mink S, Cato AC, Iniguez Lluhi JA, Baniahmad A (2002) The amino terminus of the human AR is target for corepressor action and antihormone agonism. Mol Endocrinol 16:661–673.PubMedGoogle Scholar
  53. Dutertre M, Smith CL (2003) Ligand-independent interactions of p160/steroid receptor coactivators and CREB-binding protein (CBP) with estrogen receptor-alpha: Regulation by phosphorylation sites in the A/B region depends on other receptor domains. Mol Endocrinol 17:1296–1314.PubMedGoogle Scholar
  54. Enserink JM, Christensen AE, de Rooij J, van Triest M, Schwede F, Genieser HG, Doskeland SO, Blank JL, Bos JL (2002) A novel EPAC-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol 4:901–906.PubMedGoogle Scholar
  55. Esposito G, Jaiswal BS, Xie Fet al. (2004) Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc Natl Acad Sci USA 101:2993–2998.PubMedGoogle Scholar
  56. Faber PW, van Rooij HC, Schipper HJ, Brinkmann AO, Trapman J (1993) Two different, overlapping pathways of transcription initiation are active on the TATA-less human androgen receptor promoter. The role of Sp1. J Biol Chem 268:9296–9301.Google Scholar
  57. Farini D, Puglianiello A, Mammi C, Siracusa G, Moretti C (2003) Dual effect of pituitary adenylate cyclase activating polypeptide on prostate tumor LNCaP cells: Short- and long-term exposure affect proliferation and neuroendocrine differentiation. Endocrinology 144:1631–1643.PubMedGoogle Scholar
  58. Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, Hetman J, Beavo JA, Phillips SC (2000). Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Nat Acad Sci USA 28:3702–7.Google Scholar
  59. Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311:1008–1012.PubMedGoogle Scholar
  60. Francis SH, Turko IV, Corbin JD (2001) Cyclic nucleotide phosphodiesterases: Relating structure and function. Prog Nucleic Acid Res Mol Biol 65:1–52.PubMedGoogle Scholar
  61. Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, Ogryzko V, Avantaggiati ML, Pestell RG (2000) p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. J Biol Chem 275:20853–20860.PubMedGoogle Scholar
  62. Fu M, Wang C, Wang Jet al. (2002) Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol Cell Biol 22:3373–3388.PubMedGoogle Scholar
  63. Fu M, Rao M, Wang Cet al. (2003) Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol Cell Biol 23:8563–8575.PubMedGoogle Scholar
  64. Fu M, Rao M, Wu K, Wang C, Zhang X, Hessien M, Yeung YG, Gioeli D, Weber MJ, Pestell RG (2004) The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity. J Biol Chem 279:29436–29449.PubMedGoogle Scholar
  65. Fu M, Liu M, Sauve AAet al. (2006) Hormonal control of androgen receptor function through SIRT1. Mol Cell Biol 26:8122–8135.PubMedGoogle Scholar
  66. Fuller DJ, Byus CV, Russell DH (1978) Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme. Proc Natl Acad Sci USA 75:223–227.PubMedGoogle Scholar
  67. Ghisletti S, Huang W, Ogawa S, Pascual G, Lin ME, Willson TM, Rosenfeld MG, Glass CK (2007) Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell 25:57–70.PubMedGoogle Scholar
  68. Ghosh R, Garcia GE, Crosby K, Inoue H, Thompson IM, Troyer DA, Kumar AP (2007) Regulation of cox-2 by cyclic AMP response element binding protein in prostate cancer: Potential role for nexrutine. Neoplasia 9:893–899.PubMedGoogle Scholar
  69. Gilad E, Laufer M, Matzkin H, Zisapel N (1999) Melatonin receptors in PC3 human prostate tumor cells. J Pineal Res 26:211–220.PubMedGoogle Scholar
  70. Gill G (2005) Something about SUMO inhibits transcription. Curr Opin Genet Dev 15:536–541.PubMedGoogle Scholar
  71. Gioeli D, Mandell JW, Petroni GR, Frierson HF, Jr, Weber MJ (1999) Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res 59:279–284.PubMedGoogle Scholar
  72. Gioeli D, Ficarro SB, Kwiek JJet al. (2002) Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J Biol Chem 277:29304–29314.Google Scholar
  73. Girdwood D, Bumpass D, Vaughan OA, Thain A, Anderson LA, Snowden AW, Garcia-Wilson E, Perkins ND, Hay RT (2003) P300 transcriptional repression is mediated by SUMO modification. Mol Cell 11:1043–1054.PubMedGoogle Scholar
  74. Gkonos PJ, Lokeshwar BL, Balkan W, Roos BA (1995) Neuroendocrine peptides stimulate adenyl cyclase in normal and malignant prostate cells. Regul Pept 59:43–51.PubMedGoogle Scholar
  75. Goldfarb DA, Stein BS, Shamszadeh M, Petersen RO (1986) Age-related changes in tissue levels of prostatic acid phosphatase and prostate specific antigen. J Urol 136:1266–1269.PubMedGoogle Scholar
  76. Goluboff ET, Shabsigh A, Saidi JA, Weinstein IB, Mitra N, Heitjan D, Piazza GA, Pamukcu R, Buttyan R, Olsson CA (1999) Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis. Urology 53:440–445.PubMedGoogle Scholar
  77. Goluboff ET, Prager D, Rukstalis D, Giantonio B, Madorsky M, Barken I, Weinstein IB, Partin AW, Olsson CA (2001) Safety and efficacy of exisulind for treatment of recurrent prostate cancer after radical prostatectomy. J Urol 166:882–886.UCLA Oncology Research NetworkPubMedGoogle Scholar
  78. Gong J, Zhu J, Goodman OB, Jr, Pestell RG, Schlegel PN, Nanus DM, Shen R (2006) Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells. Oncogene 25:2011–2021.PubMedGoogle Scholar
  79. Goodin JL, Rutherford CL (2002) Identification of differentially expressed genes during cyclic adenosine monophosphate-induced neuroendocrine differentiation in the human prostatic adenocarcinoma cell line LNCaP. Mol Carcinog 33:88–98.PubMedGoogle Scholar
  80. Gordge PC, Hulme MJ, Clegg RA, Miller WR (1996) Elevation of protein kinase A and protein kinase C activities in malignant as compared with normal human breast tissue. Eur J Cancer 32A:2120–2126.PubMedGoogle Scholar
  81. Goto T, Matsushima H, Kasuya Y, Hosaka Y, Kitamura T, Kawabe K, Hida A, Ohta Y, Simizu T, Takeda K (1999) The effect of papaverine on morphologic differentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells. Int J Urol 6:314–319.PubMedGoogle Scholar
  82. Gregoire S, Tremblay AM, Xiao L, Yang Q, Ma K, Nie J, Mao Z, Wu Z, Giguere V, Yang XJ (2006) Control of MEF2 transcriptional activity by coordinated phosphorylation and sumoylation. J Biol Chem 281:4423–4433.PubMedGoogle Scholar
  83. Gregory CW, Hamil KG, Kim D, Hall SH, Pretlow TG, Mohler JL, French FS (1998) Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. Cancer Res 58:5718–5724.PubMedGoogle Scholar
  84. Gregory CW, Fei X, Ponguta LA, He B, Bill HM, French FS, Wilson EM (2004) Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer. J Biol Chem 279:7119–7130.PubMedGoogle Scholar
  85. Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP (2002) Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell 9:303–313.PubMedGoogle Scholar
  86. Guo Z, Dai B, Jiang Tet al. (2006) Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell 10:309–319.PubMedGoogle Scholar
  87. Gupte RS, Weng Y, Liu L, Lee MY (2005) The second subunit of the replication factor C complex (RFC40) and the regulatory subunit (RIalpha) of protein kinase A form a protein complex promoting cell survival. Cell Cycle 4:323–329.PubMedGoogle Scholar
  88. Guthrie PD, Freeman MR, Liao ST, Chung LW (1990) Regulation of gene expression in rat prostate by androgen and beta-adrenergic receptor pathways. Mol Endocrinol 4:1343–1353.PubMedGoogle Scholar
  89. Gutierrez-Canas I, Juarranz MG, Collado B, Rodriguez-Henche N, Chiloeches A, Prieto JC, Carmena MJ (2005) Vasoactive intestinal peptide induces neuroendocrine differentiation in the LNCaP prostate cancer cell line through PKA, ERK, and PI3K. Prostate 63:44–55.PubMedGoogle Scholar
  90. Han H, Stessin A, Roberts Jet al. (2005) Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils. J Exp Med 202:353–361.PubMedGoogle Scholar
  91. Hay RT (2005) SUMO: A history of modification. Mol Cell 18:1–12.PubMedGoogle Scholar
  92. He B, Wilson EM (2002) The NH(2)-terminal and carboxyl-terminal interaction in the human androgen receptor. Mol Genet Metab 75:293–298.PubMedGoogle Scholar
  93. Heemers HV, Tindall DJ (2007) Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev 28:778–808.PubMedGoogle Scholar
  94. Hess KC, Jones BH, Marquez Bet al. (2005) The “soluble” adenylyl cyclase in sperm mediates multiple signaling events required for fertilization. Dev Cell 9:249–259.PubMedGoogle Scholar
  95. Hietakangas V, Ahlskog JK, Jakobsson AM, Hellesuo M, Sahlberg NM, Holmberg CI, Mikhailov A, Palvimo JJ, Pirkkala L, Sistonen L (2003) Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1. Mol Cell Biol 23:2953–2968.PubMedGoogle Scholar
  96. Hilz H, Tarnowski W (1970) Opposite effects of cyclic AMP and its dibutyryl derivative on glycogen levels in HeLa cells. Biochem Biophys Res Commun 40:973–981.PubMedGoogle Scholar
  97. Hong H, Yang L, Stallcup MR (1999) Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem 274:22618–22626.PubMedGoogle Scholar
  98. Hoosein NM, Logothetis CJ, Chung LW (1993) Differential effects of peptide hormones bombesin, vasoactive intestinal polypeptide and somatostatin analog RC-160 on the invasive capacity of human prostatic carcinoma cells. J Urol 149:1209–1213.PubMedGoogle Scholar
  99. Huber PR, Schnell Y, Hering F, Rutishauser G (1987) Prostate specific antigen. Experimental and clinical observations. Scand J Urol Nephrol Suppl 104:33–39.Google Scholar
  100. Huss JM, Kopp RP, Kelly DP (2002) Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem 277:40265–40274.Google Scholar
  101. Ikonen T, Palvimo JJ, Kallio PJ, Reinikainen P, Janne OA (1994) Stimulation of androgen-regulated transactivation by modulators of protein phosphorylation. Endocrinology 135:1359–1366.PubMedGoogle Scholar
  102. Jaiswal BS, Conti M (2003) Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa. Proc Natl Acad Sci USA 100:10676–10681.PubMedGoogle Scholar
  103. Jenster G, Trapman J, Brinkmann AO (1993) Nuclear import of the human androgen receptor. Biochem J 293 (Pt 3):761–768.PubMedGoogle Scholar
  104. Jenster G, van der Korput HA, Trapman J, Brinkmann AO (1995) Identification of two transcription activation units in the N-terminal domain of the human androgen receptor. J Biol Chem 270:7341–7346.PubMedGoogle Scholar
  105. Johannessen M, Delghandi MP, Moens U (2004) What turns CREB on? Cell Signal 16:1211–1227.PubMedGoogle Scholar
  106. Jongsma J, Oomen MH, Noordzij MA, Romijn JC, van Der Kwast TH, Schroder FH, van Steenbrugge GJ (2000) Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines. Prostate 42:34–44.PubMedGoogle Scholar
  107. Juang HH (2004) Nitroprusside stimulates mitochondrial aconitase gene expression through the cyclic adenosine 3′,5′-monosphosphate signal transduction pathway in human prostate carcinoma cells. Prostate 61:92–102.PubMedGoogle Scholar
  108. Juarranz MG, Bodega G, Prieto JC, Guijarro LG (2001) Vasoactive intestinal peptide (VIP) stimulates rat prostatic epithelial cell proliferation. Prostate 47:285–292.PubMedGoogle Scholar
  109. Kallen J, Schlaeppi JM, Bitsch F, Filipuzzi I, Schilb A, Riou V, Graham A, Strauss A, Geiser M, Fournier B (2004) Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): Crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha. J Biol Chem 279:49330–49337.PubMedGoogle Scholar
  110. Kallio PJ, Palvimo JJ, Mehto M, Janne OA (1994) Analysis of androgen receptor-DNA interactions with receptor proteins produced in insect cells. J Biol Chem 269:11514–11522.PubMedGoogle Scholar
  111. Kamenetsky M, Middelhaufe S, Bank EM, Levin LR, Buck J, Steegborn C (2006) Molecular details of cAMP generation in mammalian cells: A tale of two systems. J Mol Biol 362:623–639.PubMedGoogle Scholar
  112. Kang G, Chepurny OG, Malester B, Rindler MJ, Rehmann H, Bos JL, Schwede F, Coetzee WA, Holz GG (2006a) cAMP sensor EPAC as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells. J Physiol 573:595–609.Google Scholar
  113. Kang J, Gocke CB, Yu H (2006b) Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity. BMC Biochem 7:5.Google Scholar
  114. Kasbohm EA, Guo R, Yowell CW, Bagchi G, Kelly P, Arora P, Casey PJ, Daaka Y (2005) Androgen receptor activation by G(s) signaling in prostate cancer cells. J Biol Chem 280:11583–11589.PubMedGoogle Scholar
  115. Khatra BS, Printz R, Cobb CE, Corbin JD (1985) Regulatory subunit of cAMP-dependent protein kinase inhibits phosphoprotein phosphatase. Biochem Biophys Res Commun 130:567–573.PubMedGoogle Scholar
  116. Kim D, Gregory CW, French FS, Smith GJ, Mohler JL (2002) Androgen receptor expression and cellular proliferation during transition from androgen-dependent to recurrent growth after castration in the CWR22 prostate cancer xenograft. Am J Pathol 160:219–226.PubMedGoogle Scholar
  117. Kim J, Amano O, Wakayama T, Takahagi H, Iseki S (2001) The role of cyclic AMP response element-binding protein in testosterone-induced differentiation of granular convoluted tubule cells in the rat submandibular gland. Arch Oral Biol 46:495–507.PubMedGoogle Scholar
  118. Kim J, Jia L, Stallcup MR, Coetzee GA (2005) The role of protein kinase A pathway and cAMP responsive element-binding protein in androgen receptor-mediated transcription at the prostate-specific antigen locus. J Mol Endocrinol 34:107–118.PubMedGoogle Scholar
  119. 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.PubMedGoogle Scholar
  120. Kohler K, Louvard D, Zahraoui A (2004) Rab13 regulates PKA signaling during tight junction assembly. J Cell Biol 165:175–180.PubMedGoogle Scholar
  121. Kotaja N, Karvonen U, Janne OA, Palvimo JJ (2002) The nuclear receptor interaction domain of GRIP1 is modulated by covalent attachment of SUMO-1. J Biol Chem 277:30283–30288.PubMedGoogle Scholar
  122. Kraus S, Gioeli D, Vomastek T, Gordon V, Weber MJ (2006) Receptor for activated C kinase 1 (RACK1) and src regulate the tyrosine phosphorylation and function of the androgen receptor. Cancer Res 66:11047–11054.PubMedGoogle Scholar
  123. Kumar AP, Bhaskaran S, Ganapathy M, Crosby K, Davis MD, Kochunov P, Schoolfield J, Yeh IT, Troyer DA, Ghosh R (2007) Akt/cAMP-responsive element binding protein/cyclin D1 network: A novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate model mediated by nexrutine, a phellodendron amurense bark extract. Clin Cancer Res 13:2784–2794.PubMedGoogle Scholar
  124. Kvissel AK, Orstavik S, Oistad P, Rootwelt T, Jahnsen T, Skalhegg BS (2004) Induction of cbeta splice variants and formation of novel forms of protein kinase A type II holoenzymes during retinoic acid-induced differentiation of human NT2 cells. Cell Signal 16:577–587.PubMedGoogle Scholar
  125. Kvissel AK, Ramberg H, Eide T, Svindland A, Skalhegg BS, Tasken KA (2007) Androgen dependent regulation of protein kinase A subunits in prostate cancer cells. Cell Signal 19:401–409.PubMedGoogle Scholar
  126. Lee LF, Guan J, Qiu Y, Kung HJ (2001) Neuropeptide-induced androgen independence in prostate cancer cells: Roles of nonreceptor tyrosine kinases Etk/Bmx, src, and focal adhesion kinase. Mol Cell Biol 21:8385–8397.PubMedGoogle Scholar
  127. Leyton J, Coelho T, Coy DH, Jakowlew S, Birrer MJ, Moody TW (1998) PACAP(6–38) inhibits the growth of prostate cancer cells. Cancer Lett 125:131–139.PubMedGoogle Scholar
  128. Li H, Degenhardt B, Tobin D, Yao ZX, Tasken K, Papadopoulos V (2001) Identification, localization, and function in steroidogenesis of PAP7: A peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein. Mol Endocrinol 15:2211–2228.PubMedGoogle Scholar
  129. Li S, Shang Y (2007) Regulation of SRC family coactivators by post-translational modifications. Cell Signal 19:1101–1112.PubMedGoogle Scholar
  130. Liao S, Lin AH, Tymoczko JL (1971) Adenyl cyclase of cell nuclei isolated from rat ventral prostate. Biochim Biophys Acta 230:535–538.PubMedGoogle Scholar
  131. Lim JT, Piazza GA, Han EKet al. (1999) Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines. Biochem Pharmacol 58:1097–1107.PubMedGoogle Scholar
  132. Lim JT, Piazza GA, Pamukcu R, Thompson WJ, Weinstein IB (2003) Exisulind and related compounds inhibit expression and function of the androgen receptor in human prostate cancer cells. Clin Cancer Res 9:4972–4982.PubMedGoogle Scholar
  133. Limonta P, Moretti RM, Marelli MM, Dondi D, Parenti M, Motta M (1999) The luteinizing hormone-releasing hormone receptor in human prostate cancer cells: Messenger ribonucleic acid expression, molecular size, and signal transduction pathway. Endocrinology 140:5250–5256.PubMedGoogle Scholar
  134. Lin HK, Hu YC, Lee DK, Chang C (2004) Regulation of androgen receptor signaling by PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor through distinct mechanisms in prostate cancer cells. Mol Endocrinol 18:2409–2423.PubMedGoogle Scholar
  135. Lindzey J, Grossmann M, Kumar MV, Tindall DJ (1993) Regulation of the 5′-flanking region of the mouse androgen receptor gene by cAMP and androgen. Mol Endocrinol 7:1530–1540.PubMedGoogle Scholar
  136. Lipskaia L, Defer N, Esposito G, Hajar I, Garel MC, Rockman HA, Hanoune J (2000) Enhanced cardiac function in transgenic mice expressing a ca(2+)-stimulated adenylyl cyclase. Circ Res 86:795–801.PubMedGoogle Scholar
  137. Liu AY, Walter U, Greengard P (1981) Steroid hormones may regulate autophosphorylation of adenosine-3′,5′-monophosphate-dependent protein kinase in target tissues. Eur J Biochem 114:539–548.PubMedGoogle Scholar
  138. Loughney K, Taylor J, Florio VA (2005) 3′,5′-Cyclic nucleotide phosphodiesterase 11A: Localization in human tissues. Int J Impot Res 17:320–325.PubMedGoogle Scholar
  139. Mangan FR, Pegg AE, Mainwaring IP (1973) A reappraisal of the effects of adenosine 3′:5′-cyclic monophosphate on the function and morphology of the rat prostate gland. Biochem J 134:129–142.PubMedGoogle Scholar
  140. Mariot P, Vanoverberghe K, Lalevee N, Rossier MF, Prevarskaya N (2002) Overexpression of an alpha 1H (Cav3.2) T-type calcium channel during neuroendocrine differentiation of human prostate cancer cells. J Biol Chem 277:10824–10833.PubMedGoogle Scholar
  141. Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: Relation to neoplastic transformation. Cancer Res 59:1152–1159.PubMedGoogle Scholar
  142. McManus KJ, Hendzel MJ (2006) The relationship between histone H3 phosphorylation and acetylation throughout the mammalian cell cycle. Biochem Cell Biol 84:640–657.PubMedGoogle Scholar
  143. Miller JI, Ahmann FR, Drach GW, Emerson SS, Bottaccini MR (1992) The clinical usefulness of serum prostate specific antigen after hormonal therapy of metastatic prostate cancer. J Urol 147:956–961.PubMedGoogle Scholar
  144. Mizokami A, Yeh SY, Chang C (1994) Identification of 3′,5′-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter. Mol Endocrinol 8:77–88.PubMedGoogle Scholar
  145. Moul JW, Srivastava S, McLeod DG (1995) Molecular implications of the antiandrogen withdrawal syndrome. Semin Urol 13:157–163.PubMedGoogle Scholar
  146. Murray RM, Grill V, Crinis N, Ho PW, Davison J, Pitt P (2001) Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab 86:4133–4138.PubMedGoogle Scholar
  147. Nakhla AM, Khan MS, Rosner W (1990) Biologically active steroids activate receptor-bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3′,5′-monophosphate. J Clin Endocrinol Metab 71:398–404.PubMedGoogle Scholar
  148. Nazareth LV, Weigel NL (1996) Activation of the human androgen receptor through a protein kinase A signaling pathway. J Biol Chem 271:19900–19907.PubMedGoogle Scholar
  149. Nelson JB (2003) Endothelin inhibition: Novel therapy for prostate cancer. J Urol 170:S65–S67; discussion S67–S68.PubMedGoogle Scholar
  150. Nesterova M, Noguchi K, Park YG, Lee YN, Cho-Chung YS (2000) Compensatory stabilization of RIIbeta protein, cell cycle deregulation, and growth arrest in colon and prostate carcinoma cells by antisense-directed down-regulation of protein kinase A RIalpha protein. Clin Cancer Res 6:3434–3441.PubMedGoogle Scholar
  151. Nesterova MV, Johnson N, Cheadle C, Bates SE, Mani S, Stratakis CA, Khan IU, Gupta RK, Cho-Chung YS (2006) Autoantibody cancer biomarker: Extracellular protein kinase A. Cancer Res 66:8971–8974.PubMedGoogle Scholar
  152. Nwachukwu JC, Li W, Pineda-Torra I, Huang HY, Ruoff R, Shapiro E, Taneja SS, Logan SK, Garabedian MJ (2007) Transcriptional regulation of the androgen receptor cofactor androgen receptor trapped clone-27. Mol Endocrinol 21:2864–2876.PubMedGoogle Scholar
  153. Okutani T, Nishi N, Kagawa Y, Takasuga H, Takenaka I, Usui T, Wada F (1991) Role of cyclic AMP and polypeptide growth regulators in growth inhibition by interferon in PC-3 cells. Prostate 18:73–80.PubMedGoogle Scholar
  154. Orstavik S, Reinton N, Frengen E, Langeland BT, Jahnsen T, Skalhegg BS (2001) Identification of novel splice variants of the human catalytic subunit cbeta of cAMP-dependent protein kinase. Eur J Biochem 268:5066–5073.PubMedGoogle Scholar
  155. Orstavik S, Funderud A, Hafte TT, Eikvar S, Jahnsen T, Skalhegg BS (2005) Identification and characterization of novel PKA holoenzymes in human T lymphocytes. FEBS J 272:1559–1567.PubMedGoogle Scholar
  156. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759–763.PubMedGoogle Scholar
  157. Pastor-Soler N, Beaulieu V, Litvin TN, Da Silva N, Chen Y, Brown D, Buck J, Levin LR, Breton S (2003) Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J Biol Chem 278:49523–49529.PubMedGoogle Scholar
  158. Poukka H, Karvonen U, Janne OA, Palvimo JJ (2000) Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci USA 97:14145–14150.PubMedGoogle Scholar
  159. Poyet P, Gagne B, Labrie F (1986) Characteristics of the beta-adrenergic stimulation of adenylate cyclase activity in rat ventral prostate and its modulation by androgens. Prostate 9:237–245.PubMedGoogle Scholar
  160. Premont RT, Matsuoka I, Mattei MG, Pouille Y, Defer N, Hanoune J (1996) Identification and characterization of a widely expressed form of adenylyl cyclase. J Biol Chem 271:13900–13907.PubMedGoogle Scholar
  161. Purvis K, Rui H, Gordeladze JO, Attramadal H (1986) Hormonal activation of the adenylyl cyclases of the rat and human prostate gland. Prostate 8:11–24.PubMedGoogle Scholar
  162. Quayle SN, Mawji NR, Wang J, Sadar MD (2007) Androgen receptor decoy molecules block the growth of prostate cancer. Proc Natl Acad Sci USA 104:1331–1336.PubMedGoogle Scholar
  163. Rana S, Bisht D, Chakraborti PK (1999) Synergistic activation of yeast-expressed rat androgen receptor by modulators of protein kinase-A. J Mol Biol 286:669–681.PubMedGoogle Scholar
  164. Razzaboni B, Terner C (1988) Cyclic adenosine 3′,5′-monophosphate-phosphodiesterases in epididymis and prostate of castrate and of aged rats. Mech Ageing Dev 43:61–69.PubMedGoogle Scholar
  165. Redegeld FA, Smith P, Apasov S, Sitkovsky MV (1997) Phosphorylation of T-lymphocyte plasma membrane-associated proteins by ectoprotein kinases: Implications for a possible role for ectophosphorylation in T-cell effector functions. Biochim Biophys Acta 1328:151–165.PubMedGoogle Scholar
  166. Reid J, Kelly SM, Watt K, Price NC, McEwan IJ (2002) Conformational analysis of the androgen receptor amino-terminal domain involved in transactivation. Influence of structure-stabilizing solutes and protein-protein interactions. J Biol Chem 277:20079–20086.PubMedGoogle Scholar
  167. Reinton N, Orstavik S, Haugen TB, Jahnsen T, Tasken K, Skalhegg BS (2000) A novel isoform of human cyclic 3′,5′-adenosine monophosphate-dependent protein kinase, c alpha-s, localizes to sperm midpiece. Biol Reprod 63:607–611.PubMedGoogle Scholar
  168. Rentero C, Monfort A, Puigdomenech P (2003) Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene. Biochem Biophys Res Commun 301:686–692.PubMedGoogle Scholar
  169. Riegman PH, Vlietstra RJ, van der Korput JA, Brinkmann AO, Trapman J (1991) The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol Endocrinol 5:1921–1930.PubMedGoogle Scholar
  170. Rigas AC, Ozanne DM, Neal DE, Robson CN (2003) The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway. J Biol Chem 278:46087–46093.PubMedGoogle Scholar
  171. Rimler A, Culig Z, Levy-Rimler G, Lupowitz Z, Klocker H, Matzkin H, Bartsch G, Zisapel N (2001) Melatonin elicits nuclear exclusion of the human androgen receptor and attenuates its activity. Prostate 49:145–154.PubMedGoogle Scholar
  172. Rochette-Egly C (2003) Nuclear receptors: Integration of multiple signalling pathways through phosphorylation. Cell Signal 15:355–366.PubMedGoogle Scholar
  173. Rosenfeld MG, O'Malley BW (1970) Steroid hormones: Effects on adenyl cyclase activity and adenosine 3′,5′-momophosphate in target tissues. Science 168:253–255.PubMedGoogle Scholar
  174. Rosner W, Hryb DJ, Khan MS, Nakhla AM, Romas NA (1991) Sex hormone-binding globulin: Anatomy and physiology of a new regulatory system. J Steroid Biochem Mol Biol 40:813–820.PubMedGoogle Scholar
  175. Rowan BG, Garrison N, Weigel NL, O'Malley BW (2000) 8-Bromo-cyclic AMP induces phosphorylation of two sites in SRC-1 that facilitate ligand-independent activation of the chicken progesterone receptor and are critical for functional cooperation between SRC-1 and CREB binding protein. Mol Cell Biol 20:8720–8730.PubMedGoogle Scholar
  176. Ryan CW, Stadler WM, Vogelzang NJ (2005) A phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer. BJU Int 95:963–968.PubMedGoogle Scholar
  177. Sabbisetti VS, Chirugupati S, Thomas S, Vaidya KS, Reardon D, Chiriva-Internati M, Iczkowski KA, Shah GV (2005) Calcitonin increases invasiveness of prostate cancer cells: Role for cyclic AMP-dependent protein kinase A in calcitonin action. Int J Cancer 117:551–560.PubMedGoogle Scholar
  178. Sadar MD (1999) Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. J Biol Chem 274:7777–7783.PubMedGoogle Scholar
  179. Sadar MD, Gleave ME (2000) Ligand-independent activation of the androgen receptor by the differentiation agent butyrate in human prostate cancer cells. Cancer Res 60:5825–5831.PubMedGoogle Scholar
  180. Sadar MD, Hussain M, Bruchovsky N (1999) Prostate cancer: Molecular biology of early progression to androgen independence. Endocr Relat Cancer 6:487–502.PubMedGoogle Scholar
  181. Sainz RM, Mayo JC, Tan DX, Leon J, Manchester L, Reiter RJ (2005) Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate 63:29–43.PubMedGoogle Scholar
  182. San Agustin JT, Leszyk JD, Nuwaysir LM, Witman GB (1998) The catalytic subunit of the cAMP-dependent protein kinase of ovine sperm flagella has a unique amino-terminal sequence. J Biol Chem 273:24874–24883.PubMedGoogle Scholar
  183. Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A (2003) The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem 278:9013–9018.PubMedGoogle Scholar
  184. Seeler JS, Dejean A (2003) Nuclear and unclear functions of SUMO. Nat Rev Mol Cell Biol 4:690–699.PubMedGoogle Scholar
  185. Shah GV, Rayford W, Noble MJ, Austenfeld M, Weigel J, Vamos S, Mebust WK (1994) Calcitonin stimulates growth of human prostate cancer cells through receptor-mediated increase in cyclic adenosine 3′,5′-monophosphates and cytoplasmic Ca2+ transients. Endocrinology 134:596–602.PubMedGoogle Scholar
  186. Shalizi A, Gaudilliere B, Yuan Z, Stegmuller J, Shirogane T, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A (2006) A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311:1012–1017.PubMedGoogle Scholar
  187. Shao D, Lazar MA (1999) Modulating nuclear receptor function: May the phos be with you. J Clin Invest 103:1617–1618.PubMedGoogle Scholar
  188. Shaywitz AJ, Greenberg ME (1999) CREB: A stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861.PubMedGoogle Scholar
  189. Shima S, Kawashima Y, Hirai M, Asakura M (1980) Effects of androgens on isoproterenol-sensitive adenylate cyclase system of the rat prostate. Mol Pharmacol 18:45–48.PubMedGoogle Scholar
  190. Singhal RL, Ling GM (1969) Metabolic control mechanisms in mammalian systems. IV. Androgenic induction of hexokinase and glucose-6-phosphate dehydrogenase in rat seminal vesicles. Can J Physiol Pharmacol 47:233–239.PubMedGoogle Scholar
  191. Singhal RL, Parulekar MR, Ling GM (1971) Streptozotocin-induced diabetes and regulation of hepatic glucose metabolism. Can J Physiol Pharmacol 49:1005–1007.PubMedGoogle Scholar
  192. Sinibaldi VJ, Elza-Brown K, Schmidt Jet al. (2006) Phase II evaluation of docetaxel plus exisulind in patients with androgen independent prostate carcinoma. Am J Clin Oncol 29:395–398.PubMedGoogle Scholar
  193. Siu YT, Jin DY (2007) CREB – a real culprit in oncogenesis. FEBS J 274:3224–3232.PubMedGoogle Scholar
  194. Skalhegg BS, Tasken K (2000) Specificity in the cAMP/PKA signaling pathway. Differential expression, regulation, and subcellular localization of subunits of PKA. Front Biosci 5:D678–D693.PubMedGoogle Scholar
  195. Smigel MD (1986) Purification of the catalyst of adenylate cyclase. J Biol Chem 261:1976–1982.PubMedGoogle Scholar
  196. Smith FD, Langeberg LK, Scott JD (2006) The where's and when's of kinase anchoring. Trends Biochem Sci 31:316–323.PubMedGoogle Scholar
  197. Solomon SS, Brush JS, Kitabchi AE (1970) Divergent biological effects of adenosine and dibutyryl adenosine 3′,5′-monophosphate on the isolated fat cell. Science 169:387–388.PubMedGoogle Scholar
  198. Songyang Z, Blechner S, Hoagland N, Hoekstra MF, Piwnica-Worms H, Cantley LC (1994) Use of an oriented peptide library to determine the optimal substrates of protein kinases. Curr Biol 4:973–982.PubMedGoogle Scholar
  199. Stubbs AP, Lalani EN, Stamp GW, Hurst H, Abel P, Waxman J (1996) Second messenger up-regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines, PC-3 and DU-145. FEBS Lett 383:237–240.PubMedGoogle Scholar
  200. Sunahara RK, Taussig R (2002) Isoforms of mammalian adenylyl cyclase: Multiplicities of signaling. Mol Interv 2:168–184.PubMedGoogle Scholar
  201. Sutherland DJ, Singhal RL (1974a) Alterations in adenylate cyclase activity of the rat prostate gland. Biochim Biophys Acta 343:238–249.Google Scholar
  202. Sutherland DJ, Singhal RL (1974b) Stimulation of prostatic adenyl cyclase by dihydrotestosterone. Horm Metab Res 6:89.Google Scholar
  203. Sutherland EW, Rall TW (1958) Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem 232:1077–1091.Google Scholar
  204. Taneja SS, Ha S, Swenson NK, Torra IP, Rome S, Walden PD, Huang HY, Shapiro E, Garabedian MJ, Logan SK (2004) ART-27, an androgen receptor coactivator regulated in prostate development and cancer. J Biol Chem 279:13944–13952.PubMedGoogle Scholar
  205. Tang WJ, Krupinski J, Gilman AG (1991) Expression and characterization of calmodulin-activated (type I) adenylylcyclase. J Biol Chem 266:8595–8603.PubMedGoogle Scholar
  206. Taussig R, Gilman AG (1995) Mammalian membrane-bound adenylyl cyclases. J Biol Chem 270:1–4.PubMedGoogle Scholar
  207. Theurkauf WE, Vallee RB (1982) Molecular characterization of the cAMP-dependent protein kinase bound to microtubule-associated protein 2. J Biol Chem 257:3284–3290.PubMedGoogle Scholar
  208. Thomas JA, Singhal RL (1973) Testosterone-stimulation of adenyl cyclase and cyclic 3′,5′-adnosine monophosphate-3 H formation in rat seminal vesicles. Biochem Pharmacol 22:507–511.PubMedGoogle Scholar
  209. Thomas M, Dadgar N, Aphale A, Harrell JM, Kunkel R, Pratt WB, Lieberman AP (2004) Androgen receptor acetylation site mutations cause trafficking defects, misfolding, and aggregation similar to expanded glutamine tracts. J Biol Chem 279:8389–8395.PubMedGoogle Scholar
  210. Tiefenbach J, Novac N, Ducasse M, Eck M, Melchior F, Heinzel T (2006) SUMOylation of the corepressor N-CoR modulates its capacity to repress transcription. Mol Biol Cell 17:1643–1651.PubMedGoogle Scholar
  211. Tilley WD, Marcelli M, McPhaul MJ (1990) Expression of the human androgen receptor gene utilizes a common promoter in diverse human tissues and cell lines. J Biol Chem 265:13776–13781.PubMedGoogle Scholar
  212. Tortora G, Damiano V, Bianco C, Baldassarre G, Bianco AR, Lanfrancone L, Pelicci PG, Ciardiello F (1997) The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor. Oncogene 14:923–928.PubMedGoogle Scholar
  213. Tremblay A, Tremblay GB, Labrie F, Giguere V (1999) Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1. Mol Cell 3:513–519.PubMedGoogle Scholar
  214. Tsang BK, Singhal RL (1976) Androgenic effects on protein kinases and cyclic AMP-binding protein in the ventral prostate. Res Commun Chem Pathol Pharmacol 13:697–712.PubMedGoogle Scholar
  215. Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG (2006) Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: Present and future. Eur Urol 50:1194–207; discussion 1207.PubMedGoogle Scholar
  216. Ueda T, Bruchovsky N, Sadar MD (2002a) Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. J Biol Chem 277:7076–7085.Google Scholar
  217. Ueda T, Mawji NR, Bruchovsky N, Sadar MD (2002b) Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells. J Biol Chem 277:38087–38094.Google Scholar
  218. Unni E, Sun S, Nan B, McPhaul MJ, Cheskis B, Mancini MA, Marcelli M (2004) Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence. Cancer Res 64:7156–7168.PubMedGoogle Scholar
  219. van der Kwast TH, Schalken J, Ruizeveld de Winter JA, van Vroonhoven CC, Mulder E, Boersma W, Trapman J (1991) Androgen receptors in endocrine-therapy-resistant human prostate cancer. Int J Cancer 48:189–193.PubMedGoogle Scholar
  220. Verger A, Perdomo J, Crossley M (2003) Modification with SUMO. A role in transcriptional regulation. EMBO Rep 4:137–142.Google Scholar
  221. Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinanen R, Palmberg C, Palotie A, Tammela T, Isola J, Kallioniemi OP (1995) In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 9:401–406.PubMedGoogle Scholar
  222. Vossler MR, Yao H, York RD, Pan MG, Rim CS, Stork PJ (1997) cAMP activates MAP kinase and elk-1 through a B-raf- and Rap1-dependent pathway. Cell 89:73–82.PubMedGoogle Scholar
  223. Wang G, Jones SJ, Marra MA, Sadar MD (2006a) Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene 25:7311–7323.Google Scholar
  224. Wang H, Hang J, Shi Z, Li M, Yu D, Kandimalla ER, Agrawal S, Zhang R (2002) Antisense oligonucleotide targeted to RIalpha subunit of cAMP-dependent protein kinase (GEM231) enhances therapeutic effectiveness of cancer chemotherapeutic agent irinotecan in nude mice bearing human cancer xenografts: In vivo synergistic activity, pharmacokinetics and host toxicity. Int J Oncol 21:73–80.PubMedGoogle Scholar
  225. Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT (2006b) X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation. J Biol Chem 281:37773–37781.Google Scholar
  226. Weigel NL, Moore NL (2007) Steroid receptor phosphorylation: A key modulator of multiple receptor functions. Mol Endocrinol 21:2311–2319.PubMedGoogle Scholar
  227. Wheeler MA, Ayyagari RR, Wheeler GL, Weiss RM (2005) Regulation of cyclic nucleotides in the urinary tract. J Smooth Muscle Res 41:1–21.PubMedGoogle Scholar
  228. White PC, Shore AM, Clement M, McLaren J, Soeiro I, Lam EW, Brennan P (2006) Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB in lymphocytes. Oncogene 25:2170–2180.PubMedGoogle Scholar
  229. Wu D, Zhau HE, Huang WC, Iqbal S, Habib FK, Sartor O, Cvitanovic L, Marshall FF, Xu Z, Chung LW (2007) cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: Implication in human prostate cancer bone metastasis. Oncogene 26:5070–5077.PubMedGoogle Scholar
  230. Wu H, Sun L, Zhang Yet al. (2006) Coordinated regulation of AIB1 transcriptional activity by sumoylation and phosphorylation. J Biol Chem 281:21848–21856.PubMedGoogle Scholar
  231. Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM (1999) Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2. Mol Endocrinol 13:2151–2162.PubMedGoogle Scholar
  232. Xie Y, Wolff DW, Lin MF, Tu Y (2007) Vasoactive intestinal peptide transactivates the androgen receptor through a protein kinase A-dependent extracellular signal-regulated kinase pathway in prostate cancer LNCaP cells. Mol Pharmacol 72:73–85.PubMedGoogle Scholar
  233. Yamashita D, Yamaguchi T, Shimizu M, Nakata N, Hirose F, Osumi T (2004) The transactivating function of peroxisome proliferator-activated receptor gamma is negatively regulated by SUMO conjugation in the amino-terminal domain. Genes Cells 9:1017–1029.PubMedGoogle Scholar
  234. Yan C, Zhao AZ, Bentley JK, Beavo JA (1996) The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner. J Biol Chem 271:25699–25706.PubMedGoogle Scholar
  235. Yan SZ, Huang ZH, Andrews RK, Tang WJ (1998) Conversion of forskolin-insensitive to forskolin-sensitive (mouse-type IX) adenylyl cyclase. Mol Pharmacol 53:182–187.PubMedGoogle Scholar
  236. Yang CS, Vitto MJ, Busby SAet al. (2005) Simian virus 40 small t antigen mediates conformation-dependent transfer of protein phosphatase 2A onto the androgen receptor. Mol Cell Biol 25:1298–1308.PubMedGoogle Scholar
  237. Yang CS, Xin HW, Kelley JB, Spencer A, Brautigan DL, Paschal BM (2007) Ligand binding to the androgen receptor induces conformational changes that regulate phosphatase interactions. Mol Cell Biol 27:3390–3404.PubMedGoogle Scholar
  238. Yang WL, Iacono L, Tang WM, Chin KV (1998) Novel function of the regulatory subunit of protein kinase A: Regulation of cytochrome c oxidase activity and cytochrome c release. Biochemistry 37:14175–14180.PubMedGoogle Scholar
  239. Yeager RE, Heideman W, Rosenberg GB, Storm DR (1985) Purification of the calmodulin-sensitive adenylate cyclase from bovine cerebral cortex. Biochemistry 24:3776–3783.PubMedGoogle Scholar
  240. Young CY, Montgomery BT, Andrews PE, Qui SD, Bilhartz DL, Tindall DJ (1991) Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP. Cancer Res 51:3748–3752.PubMedGoogle Scholar
  241. Yuasa K, Kotera J, Fujishige K, Michibata H, Sasaki T, Omori K (2000) Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. J Biol Chem 275:31469–31479.PubMedGoogle Scholar
  242. Zegarra-Moro OL, Schmidt LJ, Huang H, Tindall DJ (2002) Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res 62:1008–1013.PubMedGoogle Scholar
  243. Zhou ZX, Sar M, Simental JA, Lane MV, Wilson EM (1994) A ligand-dependent bipartite nuclear targeting signal in the human androgen receptor. Requirement for the DNA-binding domain and modulation by NH2-terminal and carboxyl-terminal sequences. J Biol Chem 269:13115–13123.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Genome Sciences CenterBC Cancer AgencyVancouverCanada

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