Activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and serum- And glucocorticoid-induced protein kinase 1 (SGK1) by short-chain sphingolipid C4-ceramide rescues the trafficking defect of &x25b5;F508-cystic fibrosis transmembrane conductance regulator (&x25b5;F508-CFTR)

Journal of Biological Chemistry

Volumn 289, Issue 52, 2014, Pages 35953-35968

  Caohuy, Hung ^a   Yang, Qingfeng ^a   Eudy, Yvonne ^a   Ha, Thien An ^a   Xu, Andrew E ^a   Glover, Matthew ^b   Frizzell, Raymond A ^b   Jozwik, Catherine ^a   Pollard, Harvey B ^a  

^a Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL MEMBRANES; CERAMIDES; CHEMICAL ACTIVATION; CHLORINE COMPOUNDS; DEFECTS; ENZYMES; HORMONES; PHYSIOLOGY; PROTEINS; SIGNALING;

3-PHOSPHOINOSITIDE-DEPENDENT KINASE 1; APICAL PLASMA MEMBRANE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATORS; MECHANISTIC STUDIES; PRIMARY EPITHELIAL CELLS; TARGET OF RAPAMYCIN; THERAPEUTIC STRATEGY; TRANS-MEMBRANE CONDUCTANCE;

CELL SIGNALING;

2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 2 MORPHOLINO 8 PHENYLCHROMONE; CHLORIDE CHANNEL; CYCLIC AMP ACTIVATED CHLORIDE CHANNEL; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; INTERLEUKIN 8; N ACETOYL DEXTRO ERYTHRO SPHINGOSINE; N BEHENOYL DEXTRO ERYTHRO SPHINGOSINE; N BUTYROYL DEXTRO ERYTHRO SPHINGOSINE; N HEXANOYL DEXTRO ERYTHRO SPHINGOSINE; N LAUROYL DEXTRO ERYTHRO SPHINGOSINE; N OCTANOYL DEXTRO ERYTHRO SPHINGOSINE; N PALMITOYL DEXTRO ERYTHRO SPHINGOSINE; N STEAROYL DEXTRO ERYTHRO SPHINGOSINE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; SERUM AND GLUCOCORTICOID REGULATED KINASE 1; SPHINGOSINE; UBIQUITIN PROTEIN LIGASE NEDD4; UBIQUITIN PROTEIN LIGASE NEDD4 2; UNCLASSIFIED DRUG; WORTMANNIN; CERAMIDE; CFTR PROTEIN, HUMAN; ESCRT PROTEIN; IMMEDIATE EARLY PROTEIN; N-BUTANOYLSPHINGOSINE; NEDD4 UBIQUITIN PROTEIN LIGASES; PROTEIN SERINE THREONINE KINASE; PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING) KINASE; SERUM-GLUCOCORTICOID REGULATED KINASE; UBIQUITIN PROTEIN LIGASE;

ARTICLE; AUTOPHOSPHORYLATION; CELL MEMBRANE; CELLULAR DISTRIBUTION; CHLORIDE TRANSPORT; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYSTIC FIBROSIS; CYTOKINE RELEASE; DRUG DETERMINATION; DRUG EFFECT; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME ACTIVATION; ENZYME INACTIVATION; EXPLANT; HUMAN; HUMAN CELL; IN VITRO STUDY; MTT ASSAY; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STABILITY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; CELL LINE; DRUG EFFECTS; GENE DELETION; GENETICS; METABOLISM; PHOSPHORYLATION; PRECLINICAL STUDY; SECRETION (PROCESS);

CELL LINE; CELL MEMBRANE; CERAMIDES; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG EVALUATION, PRECLINICAL; ENDOSOMAL SORTING COMPLEXES REQUIRED FOR TRANSPORT; ENZYME ACTIVATION; HUMANS; IMMEDIATE-EARLY PROTEINS; INTERLEUKIN-8; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; PROTEIN TRANSPORT; PROTEIN-SERINE-THREONINE KINASES; SEQUENCE DELETION; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; UBIQUITIN-PROTEIN LIGASES;

EID: 84919808164     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.598649     Document Type: Article

References (58)

1. Riordan, J. R. (1999) Cystic fibrosis as a disease of misprocessing of the cystic fibrosis transmembrane conductance regulator protein. Am. J. Hum. Genet. 64, 1499-1504
2. Anderson, M. P., Sheppard, D. N., Berger, H. A., and Welsh, M. J. (1992) Chloride channel in the apical membrane of normal and cystic fibrosis airway and intestinal epithelia. Am. J. Physiol. 263, L1-L14
3. Srivastava, M., Eidelman, O., Zhang, J., Paweletz, C., Caohuy, H., Yang, Q., Jacobson, K. A., Heldman, E., Huang, W., Jozwik, C., Pollard, B. S., and Pollard, H. B. (2004) Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 101, 7693-7698
4. 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
5. Eidelman, O., Guay-Broder, C., van Galen, P. J., Jacobson, K. A., Fox, C., Turner, R. J., Cabantchik, Z. I., and Pollard, H. B. (1992) A1 adenosinereceptor antagonists activate chloride efflux from cystic fibrosis cells. Proc. Natl. Acad. Sci. U.S.A. 89, 5562-5566
6. Vij, N., Fang, S., and Zeitlin, P. L. (2006) Selective inhibition of endoplasmic reticulum-associated degradation rescues &x25B5;F508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implications. J. Biol. Chem. 281, 17369-17378
7. Dechecchi, M. C., Nicolis, E., Bezzerri, V., Vella, A., Colombatti, M., Assael, B. M., Mettey, Y., Borgatti, M., Mancini, I., Gambari, R., Becq, F., and Cabrini, G. (2007) MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells. Am. J. Respir. Cell Mol. Biol. 36, 615-624
8. Cholon, D. M., O'Neal, W. K., Randell, S. H., Riordan, J. R., and Gentzsch, M. (2010) Modulation of endocytic trafficking and apical stability of CFTR in primary human airway epithelial cultures. Am. J. Physiol. Lung Cell Mol. Physiol. 298, L304-L314
9. Pedemonte, N., Zegarra-Moran, O., and Galietta, L. J. (2011) Highthroughput screening of libraries of compounds to identify CFTR modulators. Methods Mol. Biol. 741, 13-21
10. Caohuy, H., Jozwik, C., and Pollard, H. B. (2009) Rescue of &x25B5;F508-CFTR by the SGK1/Nedd4-2 signaling pathway. J. Biol. Chem. 284, 25241-25253
11. Bhattacharyya, S., Balakathiresan, N. S., Dalgard, C., Gutti, U., Armistead, D., Jozwik, C., Srivastava, M., Pollard, H. B., and Biswas, R. (2011) Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyperexpression of IL-8. J. Biol. Chem. 286, 11604-11615
12. Sheppard, K., Kinross, K. M., Solomon, B., Pearson, R. B., and Phillips, W. A. (2012) Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit. Rev. Oncog. 17, 69-95
13. Kobayashi, T., and Cohen, P. (1999) Activation of serum- and glucocorti-coid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein ki-nase-1 (PDK1) and PDK2. Biochem. J. 339, 319-328
14. García-Martínez, J. M., and Alessi, D. R. (2008) mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1) Biochem. J. 416, 375-385
15. Casamayor, A., Torrance, P. D., Kobayashi, T., Thorner, J., and Alessi, D. R. (1999) Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr. Biol. 9, 186-197
16. Friant, S., Lombardi, R., Schmelzle, T., Hall, M. N., and Riezman, H. (2001) Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast. EMBO J. 20, 6783-6792
17. Ji, L., Zhang, G., Uematsu, S., Akahori, Y., and Hirabayashi, Y. (1995) Induction of apoptotic DNA fragmentation and cell death by natural ceramide. FEBS Lett. 358, 211-214
18. Gomez-Muñoz, A., Frago, L. M., Alvarez, L., and Varela-Nieto, I. (1997) Stimulation ofDNAsynthesis by natural ceramide 1-phosphate. Biochem. J. 325, 435-440
19. Paris, F., Grassmé, H., Cremesti, A., Zager, J., Fong, Y., Haimovitz-Fried-man, A., Fuks, Z., Gulbins, E., and Kolesnick, R. (2001) Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes. J. Biol. Chem. 276, 8297-8305
20. Ardail, D., Popa, I., Bodennec, J., Famy, C., Louisot, P., and Portoukalian, J. (2002) Subcellular distribution and metabolic fate of exogenous ceramides taken up by HL-60 cells. Biochim. Biophys. Acta 1583, 305-310
21. Pettus, B. J., Bielawska, A., Subramanian, P., Wijesinghe, D. S., Maceyka, M., Leslie, C. C., Evans, J. H., Freiberg, J., Roddy, P., Hannun, Y. A., and Chalfant, C. E. (2004) Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2. J. Biol. Chem. 279, 11320-11326
22. Pettus, B. J., Kitatani, K., Chalfant, C. E., Taha, T. A., Kawamori, T., Bielawski, J., Obeid, L. M., and Hannun, Y. A. (2005) The coordination of prostaglandin E2 production by sphingosine-1-phosphate and ceramide-1-phosphate. Mol. Pharmacol. 68, 330-335
23. Novgorodov, S. A., Gudz, T. I., and Obeid, L. M. (2008) Long-chain ceramide is a potent inhibitor of the mitochondrial permeability transition pore. J. Biol. Chem. 283, 24707-24717
24. Wijesinghe, D. S., Subramanian, P., Lamour, N. F., Gentile, L. B., Granado, M. H., Bielawska, A., Szulc, Z., Gomez-Munoz, A., and Chalfant, C. E. (2009) Chain length specificity for activation of cPLA2αby C1P: use of the dodecane delivery system to determine lipid-specific effects. J. Lipid Res. 50, 1986-1995
25. Babenko, N., Hassouneh, L., Budvytiene, M., Liesiene, J., and Geilen, C. (2010) Natural C18:0-ceramide induces cellular sphingolipid accumulation and apoptosis. WebmedCentral APOPTOSIS 1, WMC001100
26. Bielawska, A., Greenberg, M. S., Perry, D., Jayadev, S., Shayman, J. A., McKay, C., and Hannun, Y. A. (1996) (1S,2R)-D-erythro-2-(N-Myristoyl-amino)-1-phenyl-1-propanol as an inhibitor of ceramidase. J. Biol. Chem. 271, 12646-12654
27. Yatomi, Y., Ruan, F., Megidish, T., Toyokuni, T., Hakomori, S., and Igarashi, Y. (1996) N,N-Dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets. Biochemistry 35, 626-633
28. Merrill, A. H., Jr., van Echten, G., Wang, E., and Sandhoff, K. (1993) Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ. J. Biol. Chem. 268, 27299-27306
29. Li, L., Ståhlman, M., Rutberg, M., Håversen, L., Fogelstrand, P., Andersson, L., Levin, M., and Borén, J. (2013) ARF6 regulates neuron differentiation through glucosyl-ceramide synthase. PLoS One 8, e60118
30. Graf, C., Rovina, P., and Bornancin, F. (2009) A secondary assay for ceramide kinase inhibitors based on cell growth inhibition by short-chain ceramides. Anal. Biochem. 384, 166-169
31. Arcaro, A., and Wymann, M. P. (1993) Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. Biochem. J. 296, 297-301
32. Vlahos, C. J., Matter, W. F., Hui, K. Y., and Brown, R. F. (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269, 5241-5248
33. Raynaud, F. I., Eccles, S., Clarke, P. A., Hayes, A., Nutley, B., Alix, S., Henley, A., Di-Stefano, F., Ahmad, Z., Guillard, S., Bjerke, L. M., Kelland, L., Valenti, M., Patterson, L., Gowan, S., de Haven Brandon, A., Hayakawa, M., Kaizawa, H., Koizumi, T., Ohishi, T., Patel, S., Saghir, N., Parker, P., Waterfield, M., and Workman, P. (2007) Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res. 67, 5840-5850
34. Najafov, A., Sommer, E. M., Axten, J. M., Deyoung, M. P., and Alessi, D. R. (2011) Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem. J. 433, 357-369
35. Sherk, A. B., Frigo, D. E., Schnackenberg, C. G., Bray, J. D., Laping, N. J., Trizna, W., Hammond, M., Patterson, J. R., Thompson, S. K., Kazmin, D., Norris, J. D., and McDonnell, D. P. (2008) Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer Res. 68, 7475-7483
36. Holleran, J. P., Glover, M. L., Peters, K. W., Bertrand, C. A., Watkins, S. C., Jarvik, J. W., and Frizzell, R. A. (2012) Pharmacological rescue of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) detected by use of a novel fluorescence platform. Mol. Med. 18, 685-696
37. Van Goor, F., Hadida, S., Grootenhuis, P. D., Burton, B., Stack, J. H., Straley, K. S., Decker, C. J., Miller, M., McCartney, J., Olson, E. R., Wine, J. J., Frizzell, R. A., Ashlock, M., and Negulescu, P. A. (2011) Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc. Natl. Acad. Sci. U.S.A. 108, 18843-18848
38. Lukacs, G. L., Chang, X. B., Bear, C., Kartner, N., Mohamed, A., Riordan, J. R., and Grinstein, S. (1993) The &x25B5;F508 mutation decreases the stability of cystic fibrosis trans-membrane conductance regulator in the plasma membrane: determination of functional half-lives on transfected cells. J. Biol. Chem. 268, 21592-21598
39. Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2010) The V510D suppressor mutation stabilizes &x25B5;F508-CFTR at the cell surface. Biochemistry 49, 6352-6357
40. Conese, M. (2011) Cystic fibrosis and the innate immune system: therapeutic implications. Endocr. Metab. Immune Disord. Drug Targets 11, 8-22
41. Rottner, M., Kunzelmann, C., Mergey, M., Freyssinet, J. M., and Martínez, M. C. (2007) Exaggerated apoptosis and NF-B activation in pancreatic and tracheal cystic fibrosis cells. FASEB J. 21, 2939-2948
42. Davis, P. B., Drumm, M., and Konstan, M. W. (1996) Cystic fibrosis. Am. J. Respir. Crit. Care Med. 154, 1229-1256
43. Casamayor, A., Morrice, N. A., and Alessi, D. R. (1999) Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem. J. 342, 287-292
44. Chen, H., Nystrom, F. H., Dong, L. Q., Li, Y., Song, S., Liu, F., and Quon, M. J. (2001) Insulin stimulates increased catalytic activity of phospho-inositide-dependent kinase-1 by a phosphorylation-dependent mechanism. Biochemistry 40, 11851-11859
45. Pearce, L. R., Komander, D., and Alessi, D. R. (2010) The nuts and bolts of AGC protein kinases. Nat. Rev. Mol. Cell Biol. 11, 9-22.
46. + channel through convergent phosphorylation of Nedd4-2. J. Biol. Chem. 279, 45753-45758
47. Murray, J. T., Campbell, D. G., Morrice, N., Auld, G. C., Shpiro, N., Marquez, R., Peggie, M., Bain, J., Bloomberg, G. B., Grahammer, F., Lang, F., Wulff, P., Kuhl, D., and Cohen, P. (2004) Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochem. J. 384, 477-488
48. Frödin, M., Jensen, C. J., Merienne, K., and Gammeltoft, S. (2000) A phos-phoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1. EMBO J. 19, 2924-2934
49. Biondi, R. M., Kieloch, A., Currie, R. A., Deak, M., and Alessi, D. R. (2001) The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB. EMBO J. 20, 4380-4390
50. Sato, J. D., Chapline, M. C., Thibodeau, R., Frizzell, R. A., and Stanton, B. A. (2007) Regulation of human cystic fibrosis transmembrane conductance regulator (CFTR) by serum- and glucocorticoid-inducible kinase (SGK1). Cell Physiol. Biochem. 20, 91-98
51. Guilbault, C., De Sanctis, J. B., Wojewodka, G., Saeed, Z., Lachance, C., Skinner, T. A., Vilela, R. M., Kubow, S., Lands, L. C., Hajduch, M., Matouk, E., and Radzioch, D. (2008) Fenretinide corrects newly found ceramide deficiency in cystic fibrosis. Am. J. Respir. Cell Mol. Biol. 38, 47-56
52. Guilbault, C., Wojewodka, G., Saeed, Z., Hajduch, M., Matouk, E., De Sanctis, J. B., and Radzioch, D. (2009) Cystic fibrosis fatty acid imbalance is linked to ceramide deficiency and corrected by fenretinide. Am. J. Respir. Cell Mol. Biol. 41, 100-106
53. Teichgräber, V., Ulrich, M., Endlich, N., Riethmüller, J., Wilker, B., De Oliveira-Munding, C. C., van Heeckeren, A. M., Barr, M. L., von Kürthy, G., Schmid, K. W., Weller, M., Tümmler, B., Lang, F., Grassme, H., Döring, G., and Gulbins, E. (2008) Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med. 14, 382-391
54. Gault, C. R., Obeid, L. M., and Hannun, Y. A. (2010) An overview of sphingolipid metabolism: from synthesis to breakdown. Adv. Exp. Med. Biol. 688, 1-23
55. Rutherford, A. C., Traer, C., Wassmer, T., Pattni, K., Bujny, M. V., Carlton, J. G., Stenmark, H., and Cullen, P. J. (2006) The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport. J. Cell Sci. 119, 3944-3957
56. Pakladok, T., Almilaji, A., Munoz, C., Alesutan, I., and Lang, F. (2013) PIKfyve sensitivity of hERG channels. Cell Physiol. Biochem. 31, 785-794
57. Seebohm, G., Strutz-Seebohm, N., Birkin, R., Dell, G., Bucci, C., Spinosa, M. R., Baltaev, R., Mack, A. F., Korniychuk, G., Choudhury, A., Marks, D., Pagano, R. E., Attali, B., Pfeufer, A., Kass, R. S., Sanguinetti, M. C., Tavare, J. M., and Lang, F. (2007) Regulation of endocytic recycling of KCNQ1/ KCNE1 potassium channels. Circ. Res. 100, 686-692
58. Gentzsch, M., Chang, X. B., Cui, L., Wu, Y., Ozols, V. V., Choudhury, A., Pagano, R. E., and Riordan, J. R. (2004) Endocytic trafficking routes of wild type and &x25B5;F508 cystic fibrosis transmembrane conductance regulator. Mol. Biol. Cell 15, 2684-2696