cAMP Sensor Epac and Gastrointestinal Function

Physiology of the Gastrointestinal Tract

Volumn 2, Issue , 2012, Pages 1849-1861

  Chepurny, Oleg G ^a   Leech, Colin A ^a   Cheng, Xiaodong ^b   Holz, George G ^a  

^a SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

^b University of Texas Medical Branch School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84882534093     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-382026-6.00068-3     Document Type: Chapter

References (136)

1. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 1998, 396:474-477.
2. Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, et al. A family of cAMP-binding proteins that directly activate Rap1. Science 1998, 282:2275-2279.
3. Raaijmakers JH, Bos JL Specificity in Ras and Rap signaling. J Biol Chem 2009, 284:10995-10999.
4. Schmidt M, Evellin S, Weernink PA, von Dorp F, Rehmann H, Lomasney JW, et al. A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nat Cell Biol 2001, 3:1020-1024.
5. de Rooij J, Rehmann H, van Triest M, Cool RH, Wittinghofer A, Bos JL Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J Biol Chem 2000, 275:20829-20836.
6. Rehmann H, Arias-Palomo E, Hadders MA, Schwede F, Llorca O, Bos JL Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B. Nature 2008, 455:124-127.
7. Rehmann H, Das J, Knipscheer P, Wittinghofer A, Bos JL Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state. Nature 2006, 439:625-628.
8. Rehmann H, Prakash B, Wolf E, Rueppel A, de Rooij J, Bos JL, et al. Structure and regulation of the cAMP-binding domains of Epac2. Nat Struct Biol 2003, 10:26-32.
9. Rehmann H, Rueppel A, Bos JL, Wittinghofer A Communication between the regulatory and the catalytic region of the cAMP-responsive guanine nucleotide exchange factor Epac. J Biol Chem 2003, 278:23508-23514.
10. Bos JL Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 2003, 4:733-738.
11. Bos JL Epac proteins: multi-purpose cAMP targets. Trends Biochem Sci 2006, 31:680-686.
12. Cheng X, Ji Z, Tsalkova T, Mei F Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin (Shanghai) 2008, 40:651-662.
13. Gloerich M, Bos JL Epac: defining a new mechanism for cAMP action. Annu Rev Pharmacol Toxicol 2010, 50:355-375.
14. Holz GG New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells. Horm Metab Res 2004, 36:787-794.
15. 2+ and G protein-coupled receptors in the pancreatic beta-cell: a computational approach". Am J Physiol Cell Physiol 2008, 294:C4-6.
16. Holz GG, Kang G, Harbeck M, Roe MW, Chepurny OG Cell physiology of cAMP sensor Epac. J Physiol 2006, 577:5-15.
17. Metrich M, Berthouze M, Morel E, Crozatier B, Gomez AM, Lezoualc'h F Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology. Pflugers Arch 2010, 459:535-546.
18. Roscioni SS, Elzinga CR, Schmidt M Epac: effectors and biological functions. Naunyn Schmiedebergs Arch Pharmacol 2008, 377:345-357.
19. Seino S, Shibasaki T PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 2005, 85:1303-1342.
20. - channels in rat hepatocytes. J Physiol 2006, 573:611-625.
21. Kang G, Chepurny OG, Malester B, Rindler MJ, Rehmann H, Bos JL, et al. cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells. J Physiol 2006, 573:595-609.
22. Kang G, Leech CA, Chepurny OG, Coetzee WA, Holz GG Role of the cAMP sensor Epac as a determinant of K-ATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells. J Physiol 2008, 586:1307-1319.
23. + channels in cerebellar neurons. Proc Natl Acad Sci USA 2007, 104:2519-2524.
24. Honegger KJ, Capuano P, Winter C, Bacic D, Stange G, Wagner CA, et al. Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC). Proc Natl Acad Sci USA 2006, 103:803-808.
25. Wang Y, Klein JD, Blount MA, Martin CF, Kent KJ, Pech V, et al. Epac regulates UT-A1 to increase urea transport in inner medullary collecting ducts. J Am Soc Nephrol 2009, 20:2018-2024.
26. 2+ release in INS-1 pancreatic beta-cells. J Physiol 2001, 536:375-385.
27. 2+ release and exocytosis in pancreatic beta-cells. J Biol Chem 2003, 278:8279-8285.
28. Liu G, Jacobo SM, Hilliard N, Hockerman GH Differential modulation of Cav1.2 and Cav1.3-mediated glucose-stimulated insulin secretion by cAMP in INS-1 cells: distinct roles for exchange protein directly activated by cAMP 2 (Epac2) and protein kinase A. J Pharmacol Exp Ther 2006, 318:152-160.
29. (2+)/calmodulin kinase II after beta(1)-adrenergic receptor stimulation. J Cell Biol 2010, 189:573-587.
30. 2+ mobilization in cardiac myocytes. J Biol Chem 2007, 282:5488-5495.
31. 2+/calmodulin kinase signalling pathway in rat cardiac myocytes. J Physiol 2007, 583:685-694.
32. 2+ mobilization and exocytosis in inner medullary collecting duct. Am J Physiol Renal Physiol 2006, 291:F882-890.
33. Branham MT, Mayorga LS, Tomes CN Calcium-induced acrosomal exocytosis requires cAMP acting through a protein kinase A-independent, Epac-mediated pathway. J Biol Chem 2006, 281:8656-8666.
34. Eliasson L, Ma X, Renstrom E, Barg S, Berggren PO, Galvanovskis J, et al. SUR1 regulates PKA-independent cAMP-induced granule priming in mouse pancreatic B-cells. J Gen Physiol 2003, 121:181-197.
35. Kashima Y, Miki T, Shibasaki T, Ozaki N, Miyazaki M, Yano H, et al. Critical role of cAMP-GEFII-Rim2 complex in incretin-potentiated insulin secretion. J Biol Chem 2001, 276:46046-46053.
36. Ozaki N, Shibasaki T, Kashima Y, Miki T, Takahashi K, Ueno H, et al. cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol 2000, 2:805-811.
37. Sakaba T, Neher E Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse. Nature 2003, 424:775-778.
38. 2+-dependent exocytosis through both PKA and Epac2 in mouse melanotrophs from pituitary tissue slices. J Physiol 2005, 567:799-813.
39. Zhong N, Zucker RS cAMP acts on exchange protein activated by cAMP/cAMP-regulated guanine nucleotide exchange protein to regulate transmitter release at the crayfish neuromuscular junction. J Neurosci 2005, 25:208-214.
40. Rangarajan S, Enserink JM, Kuiperij HB, de Rooij J, Price LS, Schwede F, et al. Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the beta 2-adrenergic receptor. J Cell Biol 2003, 160:487-493.
41. Cullere X, Shaw SK, Andersson L, Hirahashi J, Luscinskas FW, Mayadas TN Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase. Blood 2005, 105:1950-1955.
42. Fukuhara S, Sakurai A, Sano H, Yamagishi A, Somekawa S, Takakura N, et al. Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway. Mol Cell Biol 2005, 25:136-146.
43. Kooistra MR, Corada M, Dejana E, Bos JL Epac1 regulates integrity of endothelial cell junctions through VE-cadherin. FEBS Lett 2005, 579:4966-4972.
44. Somekawa S, Fukuhara S, Nakaoka Y, Fujita H, Saito Y, Mochizuki N Enhanced functional gap junction neoformation by protein kinase A-dependent and Epac-dependent signals downstream of cAMP in cardiac myocytes. Circ Res 2005, 97:655-662.
45. Lotfi S, Li Z, Sun J, Zuo Y, Lam PP, Kang Y, et al. Role of the exchange protein directly activated by cyclic adenosine 5'-monophosphate (Epac) pathway in regulating proglucagon gene expression in intestinal endocrine L cells. Endocrinology 2006, 147:3727-3736.
46. Morel E, Marcantoni A, Gastineau M, Birkedal R, Rochais F, Garnier A, et al. cAMP-binding protein Epac induces cardiomyocyte hypertrophy. Circ Res 2005, 97:1296-1304.
47. O'Neill JS, Maywood ES, Chesham JE, Takahashi JS, Hastings MH cAMP-dependent signaling as a core component of the mammalian circadian pacemaker. Science 2008, 320:949-953.
48. Metrich M, Laurent AC, Breckler M, Duquesnes N, Hmitou I, Courillau D, et al. Epac activation induces histone deacetylase nuclear export via a Ras-dependent signalling pathway. Cell Signal 2010, 22:1459-1468.
49. Metrich M, Lucas A, Gastineau M, Samuel JL, Heymes C, Morel E, et al. Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy. Circ Res 2008, 102:959-965.
50. Misra UK, Pizzo SV Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades. J Cell Biochem 2009, 108:998-1011.
51. Murray AJ, Shewan DA Epac mediates cyclic AMP-dependent axon growth, guidance and regeneration. Mol Cell Neurosci 2008, 38:578-588.
52. Van Kolen K, Dautzenberg FM, Verstraeten K, Royaux I, De Hoogt R, Gutknecht E, et al. Corticotropin releasing factor-induced ERK phosphorylation in AtT20 cells occurs via a cAMP-dependent mechanism requiring EPAC2. Neuropharmacology 2010, 58:135-144.
53. Kiermayer S, Biondi RM, Imig J, Plotz G, Haupenthal J, Zeuzem S, et al. Epac activation converts cAMP from a proliferative into a differentiation signal in PC12 cells. Mol Biol Cell 2005, 16:5639-5648.
54. Woolfrey KM, Srivastava DP, Photowala H, Yamashita M, Barbolina MV, Cahill ME, et al. Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines. Nat Neurosci 2009, 12:1275-1284.
55. Kwon G, Pappan KL, Marshall CA, Schaffer JE, McDaniel ML cAMP Dose-dependently prevents palmitate-induced apoptosis by both protein kinase A-and cAMP-guanine nucleotide exchange factor-dependent pathways in beta-cells. J Biol Chem 2004, 279:8938-8945.
56. Shao W, Yu Z, Fantus IG, Jin T Cyclic AMP signaling stimulates proteasome degradation of thioredoxin interacting protein (TxNIP) in pancreatic beta-cells. Cell Signal 2010, 22:1240-1246.
57. Enserink JM, Christensen AE, de Rooij J, van Triest M, Schwede F, Genieser HG, et al. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol 2002, 4:901-906.
58. Chepurny OG, Leech CA, Kelley GG, Dzhura I, Dzhura E, Li X, et al. Enhanced Rap1 activation and insulin secretagogue properties of an acetoxymethyl ester of an Epac-selective cyclic AMP analog in rat INS-1 cells: studies with 8-pCPT-2'-O-Me-cAMP-AM. J Biol Chem 2009, 284:10728-10736.
59. Vliem MJ, Ponsioen B, Schwede F, Pannekoek WJ, Riedl J, Kooistra MR, et al. 8-pCPT-2'-O-Me-cAMP-AM: an improved Epac-selective cAMP analogue. Chembiochem 2008, 9:2052-2054.
60. Chepurny OG, Kelley GG, Dzhura I, Leech CA, Roe MW, Dzhura E, et al. PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of Langerhans. Am J Physiol Endocrinol Metab 2010, 298:E622-633.
61. Leech CA, Dzhura I, Chepurny OG, Schwede F, Genieser HG, Holz GG Facilitation of beta-cell K-ATP channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac. Islets 2010, 2:72-81.
62. 2+ channel in insulin granule exocytosis. J Biol Chem 2004, 279:7956-7961.
63. 2+ signals in insulin granule exocytosis. Diabetes 2004, 53(suppl 3):S59-62.
64. Christensen AE, Selheim F, de Rooij J, Dremier S, Schwede F, Dao KK, et al. 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 2003, 278:35394-35402.
65. Dao KK, Teigen K, Kopperud R, Hodneland E, Schwede F, Christensen AE, et al. Epac1 and cAMP-dependent protein kinase holoenzyme have similar cAMP affinity, but their cAMP domains have distinct structural features and cyclic nucleotide recognition. J Biol Chem 2006, 281:21500-21511.
66. DiPilato LM, Cheng X, Zhang J Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc Natl Acad Sci USA 2004, 101:16513-16518.
67. Ponsioen B, Zhao J, Riedl J, Zwartkruis F, van der Krogt G, Zaccolo M, et al. Detecting cAMP-induced Epac activation by fluorescence resonance energy transfer: Epac as a novel cAMP indicator. EMBO Rep 2004, 5:1176-1180.
68. Nikolaev VO, Bunemann M, Hein L, Hannawacker A, Lohse MJ Novel single chain cAMP sensors for receptor-induced signal propagation. J Biol Chem 2004, 279:37215-37218.
69. 2+ and cAMP in single cells. Sci STKE 2006, 2006:l6.
70. 2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell line. J Biol Chem 2005, 280:31294-31302.
71. Hinke SA Epac2: a molecular target for sulfonylurea-induced insulin release. Sci Signal 2, pe5 2009, 4.
72. Zhang CL, Katoh M, Shibasaki T, Minami K, Sunaga Y, Takahashi H, et al. The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. Science 2009, 325:607-610.
73. Tsalkova T, Gribenko AV, Cheng X Exchange protein directly activated by cyclic AMP isoform 2 is not a direct target of sulfonylurea drugs. Assay Drug Dev Technol 2011, 9:88-91.
74. Yu S, Fan F, Flores SC, Mei F, Cheng X Dissecting the mechanism of Epac activation via hydrogen-deuterium exchange FT-IR and structural modeling. Biochemistry 2006, 45:15318-15326.
75. Brock M, Fan F, Mei FC, Li S, Gessner C, Woods VL, et al. Conformational analysis of Epac activation using amide hydrogen/deuterium exchange mass spectrometry. J Biol Chem 2007, 282:32256-32263.
76. Tsalkova T, Blumenthal DK, Mei FC, White MA, Cheng X Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities. J Biol Chem 2009, 284:23644-23651.
77. Qiao J, Mei FC, Popov VL, Vergara LA, Cheng X Cell cycle-dependent subcellular localization of exchange factor directly activated by cAMP. J Biol Chem 2002, 277:26581-26586.
78. Borland G, Gupta M, Magiera MM, Rundell CJ, Fuld S, Yarwood SJ Microtubule-associated protein 1B-light chain 1 enhances activation of Rap1 by exchange protein activated by cyclic AMP but not intracellular targeting. Mol Pharmacol 2006, 69:374-384.
79. Dodge-Kafka KL, Soughayer J, Pare GC, Carlisle Michel JJ, Langeberg LK, Kapiloff MS, et al. The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature 2005, 437:574-578.
80. Li Y, Asuri S, Rebhun JF, Castro AF, Paranavitana NC, Quilliam LA The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane. J Biol Chem 2006, 281:2506-2514.
81. Liu C, Takahashi M, Li Y, Song S, Dillon TJ, Shinde U, et al. Ras is required for the cyclic AMP-dependent activation of Rap1 via Epac2. Mol Cell Biol 2008, 28:7109-7125.
82. Liu C, Takahashi M, Li Y, Dillon TJ, Kaech S, Stork PJ The interaction of Epac1 and Ran promotes Rap1 activation at the nuclear envelope. Mol Cell Biol 2010, 30:3956-3969.
83. Gloerich M, Ponsioen B, Vliem MJ, Zhang Z, Zhao J, Kooistra MR, et al. Spatial regulation of cyclic AMP-Epac1 signaling in cell adhesion by ERM proteins. Mol Cell Biol 2010, 30:5421-5431.
84. Purves GI, Kamishima T, Davies LM, Quayle JM, Dart C Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels. J Physiol 2009, 587:3639-3650.
85. 2+ sensor in pancreatic beta-cells. Involvement of cAMP-GEFII.Rim2. Piccolo complex in cAMP-dependent exocytosis. J Biol Chem 2002, 277:50497-50502.
86. Misra UK, Kaczowka SJ, Pizzo SV Interaction between TCL1 and Epac1 in the activation of Akt kinases in plasma membranes and nuclei of 8-CPT-2-O-Me-cAMP-stimulated macrophages. Cell Signal 2008, 20:130-138.
87. Nijholt IM, Dolga AM, Ostroveanu A, Luiten PG, Schmidt M, Eisel UL Neuronal AKAP150 coordinates PKA and Epac-mediated PKB/Akt phosphorylation. Cell Signal 2008, 20:1715-1724.
88. Magiera MM, Gupta M, Rundell CJ, Satish N, Ernens I, Yarwood SJ Exchange protein directly activated by cAMP (EPAC) interacts with the light chain (LC) 2 of MAP1A. Biochem J 2004, 382:803-810.
89. Ponsioen B, Gloerich M, Ritsma L, Rehmann H, Bos JL, Jalink K Direct spatial control of Epac1 by cyclic AMP. Mol Cell Biol 2009, 29:2521-2531.
90. Niimura M, Miki T, Shibasaki T, Fujimoto W, Iwanaga T, Seino S Critical role of the N-terminal cyclic AMP-binding domain of Epac2 in its subcellular localization and function. J Cell Physiol 2009, 219:652-658.
91. Li J, O'Connor KL, Cheng X, Mei FC, Uchida T, Townsend CM, et al. Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways. Mol Endocrinol 2007, 21:159-171.
92. Hochbaum D, Hong K, Barila G, Ribeiro-Neto F, Altschuler DL Epac, in synergy with cAMP-dependent protein kinase (PKA), is required for cAMP-mediated mitogenesis. J Biol Chem 2008, 283:4464-4468.
93. 2+ release in mouse pancreatic beta cells. J Physiol 2005, 566:173-188.
94. Borland G, Bird RJ, Palmer TM, Yarwood SJ Activation of protein kinase Calpha by EPAC1 is required for the ERK-and CCAAT/enhancer-binding protein beta-dependent induction of the SOCS-3 gene by cyclic AMP in COS1 cells. J Biol Chem 2009, 284:17391-17403.
95. Idevall-Hagren O, Barg S, Gylfe E, Tengholm A cAMP mediators of pulsatile insulin secretion from glucose-stimulated single beta-cells. J Biol Chem 2010, 285:23007-23018.
96. Ostroveanu A, van der Zee EA, Eisel UL, Schmidt M, Nijholt IM Exchange protein activated by cyclic AMP 2 (Epac2) plays a specific and time-limited role in memory retrieval. Hippocampus 2010, 20:1018-1026.
97. Shibasaki T, Takahashi H, Miki T, Sunaga Y, Matsumura K, Yamanaka M, et al. Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc Natl Acad Sci USA 2007, 104:19333-19338.
98. 2+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in b-cells of phospholipase C◇ knockout mice. J Physiol 2010, 588:4871-4889.
99. Kai AK, Lam AK, Zhang X, Lai AKW, Xu A, Vanhoutte PM, et al. Targeted disruption of exchange protein directly activated by cyclic-AMP1 in mice leads to altered islet architecture and reduced b-cell distribution of GLUT-2. Diabetes 2009, 58:LB20-LB21.
100. Shimomura H, Imai A, Nashida T Evidence for the involvement of cAMP-GEF (Epac) pathway in amylase release from the rat parotid gland. Arch Biochem Biophys 2004, 431:124-128.
101. Wu CY, DiJulio DH, Jacobson KL, McKnight GS, Watson EL The contribution of AKAP5 in amylase secretion from mouse parotid acini. Am J Physiol Cell Physiol 2010, 298:C1151-1158.
102. Chaudhuri A, Husain SZ, Kolodecik TR, Grant WM, Gorelick FS Cyclic AMP-dependent protein kinase and Epac mediate cyclic AMP responses in pancreatic acini. Am J Physiol Gastrointest Liver Physiol 2007, 292:G1403-1410.
103. Sabbatini ME, Chen X, Ernst SA, Williams JA Rap1 activation plays a regulatory role in pancreatic amylase secretion. J Biol Chem 2008, 283:23884-23894.
104. Shah AU, Grant WM, Latif SU, Mannan ZM, Park AJ, Husain SZ Cyclic AMP accelerates calcium waves in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol 2008, 294:G1328-1334.
105. Ueno H, Shibasaki T, Iwanaga T, Takahashi K, Yokoyama Y, Liu LM, et al. Characterization of the gene EPAC2: structure, chromosomal localization, tissue expression, and identification of the liver-specific isoform. Genomics 2001, 78:91-98.
106. Cullen KA, McCool J, Anwer MS, Webster CR Activation of cAMP-guanine exchange factor confers PKA-independent protection from hepatocyte apoptosis. Am J Physiol Gastrointest Liver Physiol 2004, 287:G334-343.
107. Graf D, Reinehr R, Kurz AK, Fischer R, Haussinger D Inhibition of taurolithocholate 3-sulfate-induced apoptosis by cyclic AMP in rat hepatocytes involves protein kinase A-dependent and -independent mechanisms. Arch Biochem Biophys 2003, 415:34-42.
108. Sinclair EM, Yusta B, Streutker C, Baggio LL, Koehler J, Charron MJ, et al. Glucagon receptor signaling is essential for control of murine hepatocyte survival. Gastroenterology 2008, 135:2096-2106.
109. Webster CR, Usechak P, Anwer MS cAMP inhibits bile acid-induced apoptosis by blocking caspase activation and cytochrome c release. Am J Physiol Gastrointest Liver Physiol 2002, 283:G727-738.
110. Gates A, Hohenester S, Anwer MS, Webster CR cAMP-GEF cytoprotection by Src tyrosine kinase activation of phosphoinositide-3-kinase p110 beta/alpha in rat hepatocytes. Am J Physiol Gastrointest Liver Physiol 2009, 296:G764-774.
111. Usechak P, Gates A, Webster CR Activation of focal adhesion kinase and JNK contributes to the extracellular matrix and cAMP-GEF mediated survival from bile acid induced apoptosis in rat hepatocytes. J Hepatol 2008, 49:251-261.
112. Ponzetti K, King M, Gates A, Sawkat Anwer M, Webster CLR Cyclic AMP-guanine exchange factor activation inhibits JNK-dependent lipopolysaccharide-induced apoptosis in rat hepatocytes. Hepatic Medicine 2010, 2:1-11.
113. Gaudy AM, Clementi AH, Campbell JS, Smrcka AV, Mooney RA Suppressor of cytokine signaling-3 is a glucagon-inducible inhibitor of PKA activity and gluconeogenic gene expression in hepatocytes. J Biol Chem 2010, 285:41356-41365.
114. Jiang G, Zhang BB Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 2003, 284:E671-678.
115. Masyuk AI, Gradilone SA, Banales JM, Huang BQ, Masyuk TV, Lee SO, et al. Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am J Physiol Gastrointest Liver Physiol 2008, 295:G725-734.
116. Marzioni M, Alpini G, Saccomanno S, Candelaresi C, Venter J, Rychlicki C, et al. Exendin-4, a glucagon-like peptide 1 receptor agonist, protects cholangiocytes from apoptosis. Gut 2009, 58:990-997.
117. Banales JM, Masyuk TV, Gradilone SA, Masyuk AI, Medina JF, LaRusso NF The cAMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD). Hepatology 2009, 49:160-174.
118. Usynin I, Klotz C, Frevert U Malaria circumsporozoite protein inhibits the respiratory burst in Kupffer cells. Cell Microbiol 2007, 9:2610-2628.
119. Aronoff DM, Canetti C, Serezani CH, Luo M, Peters-Golden M Cutting edge: macrophage inhibition by cyclic AMP (cAMP): differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol 2005, 174:595-599.
120. Yokoyama U, Patel HH, Lai NC, Aroonsakool N, Roth DM, Insel PA The cyclic AMP effector Epac integrates pro-and anti-fibrotic signals. Proc Natl Acad Sci USA 2008, 105:6386-6391.
121. Hoque KM, Woodward OM, van Rossum DB, Zachos NC, Chen L, Leung GP, et al. Epac1 mediates protein kinase A-independent mechanism of forskolin-activated intestinal chloride secretion. J Gen Physiol 2010, 135:43-58.
122. Holz GG, Chepurny OG Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus. Curr Med Chem 2003, 10:2471-2483.
123. Kieffer TJ, Habener JF The glucagon-like peptides. Endocr Rev 1999, 20:876-913.
124. Jin T Mechanisms underlying proglucagon gene expression. J Endocrinol 2008, 198:17-28.
125. Islam D, Zhang N, Wang P, Li H, Brubaker PL, Gaisano HY, et al. Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic alpha-and intestinal L-cell lines. Am J Physiol Endocrinol Metab 2009, 296:E174-181.
126. Chu ZL, Carroll C, Alfonso J, Gutierrez V, He H, Lucman A, et al. A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinology 2008, 149:2038-2047.
127. Drucker DJ, Jin T, Asa SL, Young TA, Brubaker PL Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. Mol Endocrinol 1994, 8:1646-1655.
128. Wang P, Wang Q, Sun J, Wu J, Li H, Zhang N, et al. POU homeodomain protein Oct-1 functions as a sensor for cyclic AMP. J Biol Chem 2009, 284:26456-26465.
129. Enyeart JA, Enyeart JJ Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway. PLoS One 2009, 4:e6088.
130. + current expression in adrenocortical cells. Mol Pharmacol 2010, 77:469-482.
131. Laxman S, Riechers A, Sadilek M, Schwede F, Beavo JA Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms. Proc Natl Acad Sci USA 2006, 103:19194-19199.
132. 2+ channel-dependent exocytosis. Cell Metab 2010, 11:543-553.
133. Ma X, Zhang Y, Gromada J, Sewing S, Berggren PO, Buschard K, et al. Glucagon stimulates exocytosis in mouse and rat pancreatic alpha-cells by binding to glucagon receptors. Mol Endocrinol 2005, 19:198-212.
134. Hatakeyama H, Takahashi N, Kishimoto T, Nemoto T, Kasai H Two cAMP-dependent pathways differentially regulate exocytosis of large dense-core and small vesicles in mouse beta-cells. J Physiol 2007, 582:1087-1098.
135. Kelley GG, Chepurny OG, Schwede F, Genieser HG, Leech CA, Roe MW, et al. Glucose-dependent potentiation of mouse islet insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM. Islets 2009, 1:260-265.
136. Chu ZL, Jones RM, He H, Carroll C, Gutierrez V, Lucman A, et al. A role for beta-cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucose-dependent insulin release. Endocrinology 2007, 148:2601-2609.