Use of kinase inhibitors to correct ΔF508-CFTR function

Molecular and Cellular Proteomics

Volumn 11, Issue 9, 2012, Pages 745-757

  Trzcińska Daneluti, Agata M ^a,b   Nguyen, Leo ^a,b   Jiang, Chong ^a,b   Fladd, Christopher ^a   Uehling, David ^c   Prakesch, Michael ^c   Al awar, Rima ^c   Rotin, Daniela ^a,b  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c ONTARIO INSTITUTE FOR CANCER RESEARCH   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

1 TERT BUTYL 3 [6 (3,5 DIMETHOXYPHENYL) 2 (4 DIETHYLAMINOBUTYLAMINO)PYRIDO[2,3 D]PYRIMIDIN 7 YL]UREA; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 3 (3,5 DIBROMO 4 HYDROXYBENZYLIDENE) 1,3 DIHYDRO 5 IODO 2 INDOLONE; 3 [4 METHYL 2 (2 OXO 3 INDOLINYLMETHYLIDENYL) 3 PYRROLYL]PROPIONIC ACID; 6 (4 FLUOROPHENYL) 2,3 DIHYDRO 5 (4 PYRIDYL)IMIDAZO[2,1 B]THIAZOLE; ALSTERPAULLONE; BAY 869766; FIBROBLAST GROWTH FACTOR RECEPTOR; FPA 124; KENPAULLONE; MITOGEN ACTIVATED PROTEIN KINASE; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; N [4 (3 BROMOANILINO) 6 QUINAZOLINYL] 2 BUTYNAMIDE; NSC 735464; ORANTINIB; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN TYROSINE KINASE INHIBITOR; RAF PROTEIN; RAS PROTEIN; SARACATINIB; SYNAPTOPHYSIN; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR;

ARTICLE; BRONCHUS MUCOSA; CELL SURFACE; CHEMICAL ANALYSIS; CONTROLLED STUDY; CYSTIC FIBROSIS; FLOW CYTOMETRY; HOMOZYGOTE; HUMAN; HUMAN CELL; INTRACELLULAR SIGNALING; PRIORITY JOURNAL; SHORT CIRCUIT CURRENT;

ANIMALS; BENZAZEPINES; CELL LINE; CRICETINAE; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DOGS; GLYCOGEN SYNTHASE KINASE 3; HEK293 CELLS; HUMANS; INDOLES; ION TRANSPORT; MEMBRANE PROTEINS; PROTEIN KINASE INHIBITORS; PROTEIN TRANSPORT; PROTEIN-TYROSINE KINASES; PYRROLES; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; RNA INTERFERENCE; RNA, SMALL INTERFERING; SEQUENCE DELETION; SIGNAL TRANSDUCTION; ZEARALENONE;

EID: 84865792229     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M111.016626     Document Type: Article

References (74)

1. Boucher, R. C. (2007) Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu. Rev. Med. 58, 157-170
2. Donaldson, S. H., and Boucher, R. C. (2007) Sodium channels and cystic fibrosis. Chest 132, 1631-1636
3. Ratjen, F. A. (2009) Cystic fibrosis: pathogenesis and future treatment strategies. Respir. Care 54, 595-605
4. Riordan, J. R. (2008) CFTR function and prospects for therapy. Annu. Rev.Biochem. 77, 701-726
5. Riordan, J. R. (2005) Assembly of functional CFTR chloride channels. Annu.Rev. Physiol. 67, 701-718
6. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L., et al. (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073
7. Quinton, P. M. (2010) Role of epithelial HCO3 transport in mucin secretion: lessons from cystic fibrosis. Am. J. Physiol. Cell Physiol 299, C1222-1233
8. Kerem, B., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M., and Tsui, L. C. (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080
9. Ratjen, F., and Döring, G. (2003) Cystic fibrosis. Lancet 361, 681-689
10. Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O'Riordan, C. R., and Smith, A. E. (1990) Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63, 827-834
11. Denning, G. M., Ostedgaard, L. S., Cheng, S. H., Smith, A. E., and Welsh, M. J. (1992) Localization of cystic fibrosis transmembrane conductance regulator in chloride secretory epithelia. J. Clin. Invest. 89, 339-349
12. Du, K., Sharma, M., and Lukacs, G. L. (2005) The DeltaF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol. 12, 17-25
13. Kopito, R. R. (1999) Biosynthesis and degradation of CFTR. Physiol. Rev. 79, S167-173
14. Yang, H., Shelat, A. A., Guy, R. K., Gopinath, V. S., Ma, T., Du, K., Lukacs, G. L., Taddei, A., Folli, C., Pedemonte, N., Galietta, L. J., and Verkman, A. S. (2003) Nanomolar affinity small molecule correctors of defective Delta F508-CFTR chloride channel gating. J. Biol. Chem. 278, 35079-35085
15. Pedemonte, N., Lukacs, G. L., Du, K., Caci, E., Zegarra-Moran, O., Galietta, L. J., and Verkman, A. S. (2005) Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening. J. Clin. Invest. 115, 2564-2571
16. Carlile, G. W., Robert, R., Zhang, D., Teske, K. A., Luo, Y., Hanrahan, J. W., and Thomas, D. Y. (2007) Correctors of protein trafficking defects identified by a novel high-throughput screening assay. Chembiochem 8, 1012-1020
17. Robert, R., Carlile, G. W., Liao, J., Balghi, H., Lesimple, P., Liu, N., Kus, B., Rotin, D., Wilke, M., de Jonge, H. R., Scholte, B. J., Thomas, D. Y., and Hanrahan, J. W. (2010) Correction of the Delta phe508 cystic fibrosis transmembrane conductance regulator trafficking defect by the bioavailable compound glafenine. Mol. Pharm. 77, 922-930
18. Robert, R., Carlile, G. W., Pavel, C., Liu, N., Anjos, S. M., Liao, J., Luo, Y., Zhang, D., Thomas, D. Y., and Hanrahan, J. W. (2008) Structural analog of sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect. Mol. Pharm. 73, 478-489
19. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2005) Rescue of DeltaF508 and other misprocessed CFTR mutants by a novel quinazoline compound. Mol. Pharm 2, 407-413
20. Van Goor, F., Straley, K. S., Cao, D., González, J., Hadida, S., Hazlewood, A., Joubran, J., Knapp, T., Makings, L. R., Miller, M., Neuberger, T., Olson, E., Panchenko, V., Rader, J., Singh, A., Stack, J. H., Tung, R., Grootenhuis, P. D., and Negulescu, P. (2006) Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am. J. Physiol. 290, L1117-1130
21. Clancy, J. P., Rowe, S. M., Accurso, F. J., Aitken, M. L., Amin, R. S., Ashlock, M. A., Ballmann, M., Boyle, M. P., Bronsveld, I., Campbell, P. W., Deboeck, K., Donaldson, S. H., Dorkin, H. L., Dunitz, J. M., Durie, P. R., Jain, M., Leonard, A., McCoy, K. S., Moss, R. B., Pilewski, J. M., Rosenbluth, D. B., Rubenstein, R. C., Schechter, M. S., Botfield, M., Ordonez, C. L., Spencer-Green, G. T., Vernillet, L., Wisseh, S., Yen, K., and Konstan, M. W. (2011) Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 67, 12-18
22. Trzcinska-Daneluti, A. M., Ly, D., Huynh, L., Jiang, C., Fladd, C., and Rotin, D. (2009) High-content functional screen to identify proteins that correct F508del-CFTR function. Mol. Cell. Proteomics 8, 780-790
23. Zabner, J., Zeiher, B. G., Friedman, E., and Welsh, M. J. (1996) Adenovirusmediated gene transfer to ciliated airway epithelia requires prolonged incubation time. J. Virol. 70, 6994-7003
24. Kim Chiaw, P., Huan, L. J., Gagnon, S., Ly, D., Sweezey, N., Rotin, D., Deber, C. M., and Bear, C. E. (2009) Functional rescue of DeltaF508-CFTR by peptides designed to mimic sorting motifs. Chem. Biol. 16, 520-530
25. Ostedgaard, L. S., Zabner, J., Vermeer, D. W., Rokhlina, T., Karp, P. H., Stecenko, A. A., Randak, C., and Welsh, M. J. (2002) CFTR with a partially deleted R domain corrects the cystic fibrosis chloride transport defect in human airway epithelia in vitro and in mouse nasal mucosa in vivo. Proc. Natl. Acad. Sci. U.S.A. 99, 3093-3098
26. Bebök, Z., Venglarik, C. J., Pánczél, Z., Jilling, T., Kirk, K. L., and Sorscher, E. J. (1998) Activation of DeltaF508 CFTR in an epithelial monolayer. Am. J. Physiol. 275, C599-607
27. Shen, Y., Boivin, R., Yoneda, N., Du, H., Schiller, S., Matsushima, T., Goto, M., Shirota, H., Gusovsky, F., Lemelin, C., Jiang, Y., Zhang, Z., Pelletier, R., Ikemori-Kawada, M., Kawakami, Y., Inoue, A., Schnaderbeck, M., and Wang, Y. (2010) Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III. Bio. Med. Chem. Lett. 20, 3155-3157
28. Muramoto, K., Goto, M., Inoue, Y., Ishii, N., Chiba, K., Kuboi, Y., Omae, T., Wang, Y. J., Gusovsky, F., and Shirota, H. (2010) E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J. Pharm. Exp. Therap. 335, 23-31
29. Johnson, L. G., Olsen, J. C., Sarkadi, B., Moore, K. L., Swanstrom, R., and Boucher, R. C. (1992) Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat. Genet. 2, 21-25
30. Zhang, L., Button, B., Gabriel, S. E., Burkett, S., Yan, Y., Skiadopoulos, M. H., Dang, Y. L., Vogel, L. N., McKay, T., Mengos, A., Boucher, R. C., Collins, P. L., and Pickles, R. J. (2009) CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epithelium. PLoS Biol. 7, e1000155
31. Thomas, S. R., Jaffe, A., Geddes, D. M., Hodson, M. E., and Alton, E. W. (1999) Pulmonary disease severity in men with deltaF508 cystic fibrosis and residual chloride secretion. Lancet 353, 984-985
32. Dorin, J. R., Farley, R., Webb, S., Smith, S. N., Farini, E., Delaney, S. J., Wainwright, B. J., Alton, E. W., and Porteous, D. J. (1996) A demonstration using mouse models that successful gene therapy for cystic fibrosis requires only partial gene correction. Gene Ther. 3, 797-801
33. Fajac, I., Hubert, D., Bienvenu, T., Richaud-Thiriez, B., Matran, R., Kaplan, J. C., Dall'Ava-Santucci, J., and Dusser, D. J. (1998) Relationships between nasal potential difference and respiratory function in adults with cystic fibrosis. Eur. Respir. J. 12, 1295-1300
34. Rabeh, W. M., Bossard, F., Xu, H., Okiyoneda, T., Bagdany, M., Mulvihill, C. M., Du, K., di Bernardo, S., Liu, Y., Konermann, L., Roldan, A., and Lukacs, G. L. (2012) Correction of both NBD1 energetics and domain interface is required to restore DeltaF508 CFTR folding and function. Cell 148, 150-163
35. Laird, A. D., Christensen, J. G., Li, G., Carver, J., Smith, K., Xin, X., Moss, K. G., Louie, S. G., Mendel, D. B., and Cherrington, J. M. (2002) SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J. 16, 681-690
36. Kuenen, B. C., Giaccone, G., Ruijter, R., Kok, A., Schalkwijk, C., Hoekman, K., and Pinedo, H. M. (2005) Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. Clin. Cancer Res. 11, 6240-6246
37. Xiong, H. Q., Herbst, R., Faria, S. C., Scholz, C., Davis, D., Jackson, E. F., Madden, T., McConkey, D., Hicks, M., Hess, K., Charnsangavej, C. A., and Abbruzzese, J. L. (2004) A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest. New Drugs 22, 459-466
38. Porter, J. R., Fritz, C. C., and Depew, K. M. (2010) Discovery and development of Hsp90 inhibitors: a promising pathway for cancer therapy. Curr.Opin. Chem. Biol. 14, 412-420
39. Mohammadi, M., McMahon, G., Sun, L., Tang, C., Hirth, P., Yeh, B. K., Hubbard, S. R., and Schlessinger, J. (1997) Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276, 955-960
40. Sun, L., Tran, N., Liang, C., Tang, F., Rice, A., Schreck, R., Waltz, K., Shawver, L. K., McMahon, G., and Tang, C. (1999) Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl] indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases. J. Med. Chem. 42, 5120-5130
41. Grand, E. K., Chase, A. J., Heath, C., Rahemtulla, A., and Cross, N. C. (2004) Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074. Leukemia 18, 962-966
42. Mohammadi, M., Froum, S., Hamby, J. M., Schroeder, M. C., Panek, R. L., Lu, G. H., Eliseenkova, A. V., Green, D., Schlessinger, J., and Hubbard, S. R. (1998) Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 17, 5896-5904
43. Kubo, K., Shimizu, T., Ohyama, S., Murooka, H., Iwai, A., Nakamura, K., Hasegawa, K., Kobayashi, Y., Takahashi, N., Takahashi, K., Kato, S., Izawa, T., and Isoe, T. (2005) Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N′-{4-(4-quinolyloxy)phenyl}ureas. J. Med. Chem. 48, 1359-1366
44. Sweeney, W. E., Futey, L., Frost, P., and Avner, E. D. (1999) In vitro modulation of cyst formation by a novel tyrosine kinase inhibitor. Kidney Int. 56, 406-413
45. Iverson, C., Larson, G., Lai, C., Yeh, L. T., Dadson, C., Weingarten, P., Appleby, T., Vo, T., Maderna, A., Vernier, J. M., Hamatake, R., Miner, J. N., and Quart, B. (2009) RDEA119/BAY869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res. 69, 6839-6847
46. Barrett, S. D., Bridges, A. J., Dudley, D. T., Saltiel, A. R., Fergus, J. H., Flamme, C. M., Delaney, A. M., Kaufman, M., LePage, S., Leopold, W. R., Przybranowski, S. A., Sebolt-Leopold, J., Van Becelaere, K., Doherty, A. M., Kennedy, R. M., Marston, D., Howard, W. A., Jr., Smith, Y., Warmus, J. S., and Tecle, H. (2008) The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901. Bioorg. Med. Chem. Lett. 18, 6501-6504
47. Kolch, W. (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol. 6, 827-837
48. Shaul, Y. D., and Seger, R. (2007) The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim. Biophys. Acta 1773, 1213-1226
49. Wang, S., and Koromilas, A. E. (2009) Stat1 is an inhibitor of Ras-MAPK signaling and Rho small GTPase expression with implications in the transcriptional signature of Ras transformed cells. Cell Cycle 8, 2070-2079
50. Banerjee Mustafi, S., Chakraborty, P. K., and Raha, S. (2010) Modulation of Akt and ERK1/2 pathways by resveratrol in chronic myelogenous leukemia (CML) cells results in the downregulation of Hsp70. PLoS One 5, e8719
51. Chu, B., Soncin, F., Price, B. D., Stevenson, M. A., and Calderwood, S. K. (1996) Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1. J. Biol. Chem. 271, 30847-30857
52. Chu, B., Zhong, R., Soncin, F., Stevenson, M. A., and Calderwood, S. K. (1998) Transcriptional activity of heat shock factor 1 at 37 degrees C is repressed through phosphorylation on two distinct serine residues by glycogen synthase kinase 3 and protein kinases Calpha and Czeta. J. Biol. Chem. 273, 18640-18646
53. Nunes, S. L., and Calderwood, S. K. (1995) Heat shock factor-1 and the heat shock cognate 70 protein associate in high molecular weight complexes in the cytoplasm of NIH-3T3 cells. Biochem. Biophys. Res. Commun. 213, 1-6
54. Zou, J., Guo, Y., Guettouche, T., Smith, D. F., and Voellmy, R. (1998) Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94, 471-480
55. Jope, R. S., and Johnson, G. V. (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem. Sci 29, 95-102
56. Leost, M., Schultz, C., Link, A., Wu, Y. Z., Biernat, J., Mandelkow, E. M., Bibb, J. A., Snyder, G. L., Greengard, P., Zaharevitz, D. W., Gussio, R., Senderowicz, A. M., Sausville, E. A., Kunick, C., and Meijer, L. (2000) Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. Eur. J. Biochem. 267, 5983-5994
57. Bain, J., McLauchlan, H., Elliott, M., and Cohen, P. (2003) The specificities of protein kinase inhibitors: an update. Biochem. J. 371, 199-204
58. Xavier, I. J., Mercier, P. A., McLoughlin, C. M., Ali, A., Woodgett, J. R., and Ovsenek, N. (2000) Glycogen synthase kinase 3beta negatively regulates both DNA-binding and transcriptional activities of heat shock factor 1. J. Biol. Chem. 275, 29147-29152
59. Pirkkala, L., Nykänen, P., and Sistonen, L. (2001) Roles of the heat shock transcription factors in regulation of the heat shock response and beyond. FASEB J. 15, 1118-1131
60. Bao, X. Q., and Liu, G. T. (2009) Induction of overexpression of the 27- and 70-kDa heat shock proteins by bicyclol attenuates concanavalin A-Induced liver injury through suppression of nuclear factor-kappaB in mice. Mol. Pharm. 75, 1180-1188
61. Murapa, P., Gandhapudi, S., Skaggs, H. S., Sarge, K. D., and Woodward, J. G. (2007) Physiological fever temperature induces a protective stress response in T lymphocytes mediated by heat shock factor-1 (HSF1). J. Immunol. 179, 8305-8312
62. Rada, A., Merentes, E., Rodríguez, M., Anselmi, G., and Strauss, M. (2010) Human hepatoma cell line (HepG2) cellular response to hypothermic stress with recovery. Induction of Hsp70, Hsp60 and Hsf1 expression. Invest. Clin. 51, 479-488
63. Saito, K., Dai, Y., and Ohtsuka, K. (2005) Enhanced expression of heat shock proteins in gradually dying cells and their release from necrotically dead cells. Exp. Cell Res. 310, 229-236
64. Walsh, D., Li, Z., Wu, Y., and Nagata, K. (1997) Heat shock and the role of the HSPs during neural plate induction in early mammalian CNS and brain development. Cell. Mol. Life Sci. 53, 198-211
65. Hayashida, N., Fujimoto, M., Tan, K., Prakasam, R., Shinkawa, T., Li, L., Ichikawa, H., Takii, R., and Nakai, A. (2010) Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT. EMBO J. 29, 3459-3469
66. Parsell, D. A., and Lindquist, S. (1993) The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins. Annu. Rev. Genet. 27, 437-496
67. Choo-Kang, L. R., and Zeitlin, P. L. (2001) Induction of HSP70 promotes DeltaF508 CFTR trafficking. Am. J. Physiol. 281, L58-68
68. Banz, V. M., Medová, M., Keogh, A., Furer, C., Zimmer, Y., Candinas, D., and Stroka, D. (2009) Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta. Biochim. Biophys. Acta 1793, 1597-1603
69. Norez, C., Bilan, F., Kitzis, A., Mettey, Y., and Becq, F. (2008) Proteasomedependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutation of glycine 622. J. Pharmacol. Exp. Ther. 325, 89-99
70. Fuller, W., and Cuthbert, A. W. (2000) Post-translational disruption of the delta F508 cystic fibrosis transmembrane conductance regulator (CFTR)-molecular chaperone complex with geldanamycin stabilizes delta F508 CFTR in the rabbit reticulocyte lysate. J. Biol. Chem. 275, 37462-37468
71. Wang, X., Venable, J., LaPointe, P., Hutt, D. M., Koulov, A. V., Coppinger, J., Gurkan, C., Kellner, W., Matteson, J., Plutner, H., Riordan, J. R., Kelly, J. W., Yates, J. R., 3rd, and Balch, W. E. (2006) Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 127, 803-815
72. Tuo, B., Wen, G., Zhang, Y., Liu, X., Wang, X., and Dong, H. (2009) Involvement of phosphatidylinositol 3-kinase in cAMP- and cGMP-induced duodenal epithelial CFTR activation in mice. Am. J. Physiol. Cell Physiol. 297, C503-515
73. Jung, H. J., and Kwon, T. H. (2010) Membrane Trafficking of Collecting Duct Water Channel Protein AQP2 Regulated by Akt/AS160. Electrolyte Blood Press. 8, 59-65
74. Robertson, S. D., Matthies, H. J., Owens, W. A., Sathananthan, V., Christianson, N. S., Kennedy, J. P., Lindsley, C. W., Daws, L. C., and Galli, A. (2010) Insulin reveals Akt signaling as a novel regulator of norepinephrine transporter trafficking and norepinephrine homeostasis. J. Neurosci. 30, 11305-11316