AKT and GSK-3 are necessary for direct ezrin binding to NHE3 as part of a C-terminal Stimulatory complex: Role of a novel Ser-rich NHE3 C-Terminal motif in NHE3 activity and trafficking

Journal of Biological Chemistry

Volumn 289, Issue 9, 2014, Pages 5449-5461

  Singh, Varsha ^a   Lin, Rong ^a,b   Yang, Jianbo ^a   Cha, Boyoung ^a   Sarker, Rafiquel ^a   Tse, Chung Ming ^a   Donowitz, Mark ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

BASAL ACTIVITIES; C-TERMINAL DOMAINS; MULTI-PROTEIN COMPLEX; PHOSPHOINOSITIDES; PHOSPHORYLATION SITES; SEQUENTIAL EFFECTS; SIGNALING COMPLEX; SURFACE EXPRESSION;

AMINO ACIDS; PHOSPHOLIPIDS;

ENZYMES;

EZRIN; GLYCOGEN SYNTHASE KINASE 3; PROTEIN KINASE B; SODIUM PROTON EXCHANGE PROTEIN 3;

ALPHA HELIX; ARTICLE; BINDING SITE; CARBOXY TERMINAL SEQUENCE; COMPLEX FORMATION; CONTROLLED STUDY; EMBRYO; ENZYME INHIBITION; ENZYME REGULATION; HUMAN; HUMAN CELL; POINT MUTATION; PREDICTION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION;

ABSORPTION; AKT; ALPHA HELIX; EZRIN; MEMBRANE; NA+/H+ EXCHANGER; PHOSPHORYLATION; TRAFFICKING;

AMINO ACID MOTIFS; AMINO ACID SUBSTITUTION; ANIMALS; CYTOSKELETAL PROTEINS; ENZYME INHIBITORS; GLYCOGEN SYNTHASE KINASE 3; HEK293 CELLS; HUMANS; POINT MUTATION; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS C-AKT; RABBITS; SODIUM-HYDROGEN ANTIPORTER;

EID: 84896804088     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.521336     Document Type: Article

References (50)

1. + exchanger isoform 3 are involved in the basal and serum-stimulated membrane trafficking of the exchanger. Biochemistry 39, 1990-2000
2. Donowitz, M., Janecki, A., Akhter, S., Cavet, M. E., Sanchez, F., Lamprecht, G., Zizak, M., Kwon, W. L., Khurana, S., Yun, C. H., and Tse, C. M. (2000) Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts. Ann. N.Y. Acad. Sci. 915, 30-42 (Pubitemid 32059359)
3. + exchanger NHE3 by glucocorticoids. Mol. Biol. Cell 22, 3812-3825
4. Lee-Kwon, W., Johns, D. C., Cha, B., Cavet, M., Park, J., Tsichlis, P., and Donowitz, M. (2001) Constitutively active phosphatidylinositol 3-kinase and AKT are sufficient to stimulate the epithelial Na+/H+ exchanger 3. J. Biol. Chem. 276, 31296-31304 (Pubitemid 37385000)
5. Shiue, H., Musch, M. W., Wang, Y., Chang, E. B., and Turner, J. R. (2005) Akt2 phosphorylates ezrin to trigger NHE3 translocation and activation. J. Biol. Chem. 280, 1688-1695
6. + exchanger 3 (NHE3) occurs through changes in NHE3 trafficking and complex formation and is Src dependent. J. Physiol. 556, 791-804
7. Singh, V., Yang, J., Chen, T. E., Zachos, N. C., Kovbasnjuk, O., Verkman, A. S., and Donowitz, M. (2014) Translating molecular physiology of intestinal transport into pharmacologic treatment of diarrhea. Stimulation of Na absorption. Clin. Gastroenterol. Hepatol. 12, 27-31
8. Zachos, N. C., Hodson, C., Kovbasnjuk, O., Li, X., Thelin, W. R., Cha, B., Milgram, S., and Donowitz, M. (2008) Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism. Cell. Physiol. Biochem. 22, 693-704
9. Zachos, N. C., Li, X., Kovbasnjuk, O., Hogema, B., Sarker, R., Lee, L. J., Li, M., de Jonge, H., and Donowitz, M. (2009) NHERF3 (PDZK1) contributes to basal and calcium inhibition of NHE3 activity in Caco-2BBe cells. J. Biol. Chem. 284, 23708-23718
10. +-glucose cotransport. Proc. Natl. Acad. Sci. U.S.A. 101, 9485-9490
11. Bretscher, A., Edwards, K., and Fehon, R. G. (2002) ERM proteins and merlin. Integrators at the cell cortex. Nat. Rev. Mol. Cell Biol. 3, 586-599
12. Fiévet, B., Louvard, D., and Arpin, M. (2007) ERM proteins in epithelial cell organization and functions. Biochim. Biophys. Acta 1773, 653-660 (Pubitemid 46660175)
13. Cha, B., Tse, M., Yun, C., Kovbasnjuk, O., Mohan, S., Hubbard, A., Arpin, M., and Donowitz, M. (2006) The NHE3 juxtamembrane cytoplasmic domain directly binds ezrin. Dual role in NHE3 trafficking and mobility in the brush border. Mol. Biol. Cell 17, 2661-2673 (Pubitemid 43825503)
14. + exchanger NHE3 and the cytoskeletal protein ezrin. J. Biol. Chem. 273, 25856-25863
15. + exchanger, NHE3, requires an associated regulatory protein. Proc. Natl. Acad. Sci. U.S.A. 94, 3010-3015
16. Weinman, E. J., Steplock, D., Donowitz, M., and Shenolikar, S. (2000) NHERF associations with sodium-hydrogen exchanger isoform 3 (NHE3) and ezrin are essential for cAMP-mediated phosphorylation and inhibition of NHE3. Biochemistry 39, 6123-6129 (Pubitemid 30327087)
17. + exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation ofNHEregulatory factor. J. Biol. Chem. 274, 24753-24758
18. + antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring protein. J. Biol. Chem. 280, 16642-16650
19. + exchanger NHE3 activity and trafficking are lipid Raft-dependent. J. Biol. Chem. 281, 17845-17855
20. + exchanger isoforms (NHE1 and NHE3) in polarized epithelial cell lines. J. Cell Sci. 109, 929-939
21. Mohan, S., Tse, C. M., Gabelli, S. B., Sarker, R., Cha, B., Fahie, K., Nadella, M., Zachos, N. C., Tu-Sekine, B., Raben, D., Amzel, L. M., and Donowitz, M. (2010) NHE3 activity is dependent on direct phosphoinositide binding at the N terminus of its intracellular cytosolic region. J. Biol. Chem. 285, 34566-34578
22. Calleja, V., Laguerre, M., Parker, P. J., and Larijani, B. (2009) Role of a novel PH-kinase domain interface in PKB/Akt regulation. Structural mechanism for allosteric inhibition. PLoS Biol. 7, e17
23. Barnett, S. F., Defeo-Jones, D., Fu, S., Hancock, P. J., Haskell, K. M., Jones, R. E., Kahana, J. A., Kral, A. M., Leander, K., Lee, L. L., Malinowski, J., McAvoy, E. M., Nahas, D. D., Robinson, R. G., and Huber, H. E. (2005) Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem. J. 385, 399-408 (Pubitemid 40165072)
24. Murtazina, R., Kovbasnjuk, O., Chen, T. E., Zachos, N. C., Chen, Y., Kocinsky, H. S., Hogema, B. M., Seidler, U., de Jonge, H. R., and Donowitz, M. (2011) NHERF2 is necessary for basal activity, second messenger inhibition, and LPA stimulation of NHE3 in mouse distal ileum. Am. J. Physiol. Cell Physiol. 301, C126-C136
25. + exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. J. Biol. Chem. 277, 7676-7683
26. Gautreau, A., Louvard, D., and Arpin, M. (2000) Morphogenic effects of ezrin require a phosphorylation-induced transition from oligomers to monomers at the plasma membrane. J. Cell Biol. 150, 193-203 (Pubitemid 30480237)
27. + exchanger isoform NHE3 are involved in stimulation and inhibition by protein kinases/growth factors. J. Biol. Chem. 270, 13716-13725
28. + exchangers. An epithelial membrane-bound N-terminal domain requires an epithelial cytoplasmic C-terminal domain for regulation by protein kinases. Proc. Natl. Acad. Sci. U.S.A. 92, 10723-10727
29. + exchanger regulatory factor (NHERF) proteins. Clin. Exp. Pharmacol. Physiol. 35, 863-871
30. Welsh, G. I., Foulstone, E. J., Young, S. W., Tavaré, J. M., and Proud, C. G. (1994) Wortmannin inhibits the effects of insulin and serum on the activities of glycogen synthase kinase-3 and mitogen-activated protein kinase. Biochem. J. 303, 15-20 (Pubitemid 24302892)
31. Pap, M., and Cooper, G. M. (1998) Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J. Biol. Chem. 273, 19929-19932 (Pubitemid 28377539)
32. Coghlan, M. P., Culbert, A. A., Cross, D. A., Corcoran, S. L., Yates, J. W., Pearce, N. J., Rausch, O. L., Murphy, G. J., Carter, P. S., Roxbee Cox, L., Mills, D., Brown, M. J., Haigh, D., Ward, R. W., Smith, D. G., Murray, K. J., Reith, A. D., and Holder, J. C. (2000) Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem. Biol. 7, 793-803
33. + exchanger 3 is in large complexes in the center of the apical surface of proximal tubule-derived OK cells. Am. J. Physiol. Cell Physiol. 283, C927-C940
34. Donowitz, M., and Li, X. (2007) Regulatory binding partners and complexes of NHE3. Physiol. Rev. 87, 825-872 (Pubitemid 47086280)
35. + exchange. Annu. Rev. Physiol. 67, 411-443
36. + exchanger 3 (NHE3) and stimulates NHE3 basal activity by phosphorylating a separate site in NHE3. Mol. Biol. Cell 19, 3859-3870
37. + exchanger 3 (NHE3) by a NHERF2 protein-dependent process. J. Biol. Chem. 287, 13442-13456
38. + exchange regulatory factor 2-dependent process. Gastroenterology 140, 560-571
39. Nakamura, F., Amieva, M. R., and Furthmayr, H. (1995) Phosphorylation of threonine 558 in the carboxyl-terminal actin-binding domain of moesin by thrombin activation of human platelets. J. Biol. Chem. 270, 31377-31385 (Pubitemid 26012231)
40. Wagner, U., Utton, M., Gallo, J. M., and Miller, C. C. (1996) Cellular phosphorylation of tau by GSK-3β influences τ binding to microtubules and microtubule organisation. J. Cell Sci. 109, 1537-1543 (Pubitemid 26190502)
41. Wakefield, J. G., Stephens, D. J., and Tavaré, J. M. (2003) A role for glycogen synthase kinase-3 in mitotic spindle dynamics and chromosome alignment. J. Cell Sci. 116, 637-646 (Pubitemid 36231302)
42. Adachi, A., Kano, F., Tsuboi, T., Fujita, M., Maeda, Y., and Murata, M. (2010) Golgi-associated GSK3β regulates the sorting process of post-Golgi membrane trafficking. J. Cell Sci. 123, 3215-3225
43. Colosimo, P. F., Liu, X., Kaplan, N. A., and Tolwinski, N. S. (2010) GSK3β affects apical-basal polarity and cell-cell adhesion by regulating aPKC levels. Dev. Dyn. 239, 115-125
44. Kim, M., Datta, A., Brakeman, P., Yu, W., and Mostov, K. E. (2007) Polarity proteins PAR6 and aPKC regulate cell death through GSK-3β in 3D epithelial morphogenesis. J. Cell Sci. 120, 2309-2317 (Pubitemid 47225934)
45. Kim, S. E., Huang, H., Zhao, M., Zhang, X., Zhang, A., Semonov, M. V., MacDonald, B. T., Zhang, X.,Garcia Abreu, J., Peng, L., and He, X. (2013) Wnt stabilization of β-catenin reveals principles for morphogen receptorscaffold assemblies. Science 340, 867-870
46. Fiol, C. J., Mahrenholz, A. M., Wang, Y., Roeske, R. W., and Roach, P. J. (1987) Formation of protein kinase recognition sites by covalent modification of the substrate. Molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J. Biol. Chem. 262, 14042-14048
47. Cohen, P., and Frame, S. (2001) The renaissance of GSK3. Nat. Rev. Mol. Cell Biol. 2, 769-776 (Pubitemid 33679839)
48. Hayashi, H., Tamura, A., Krishnan, D., Tsukita, S., Suzuki, Y., Kocinsky, H. S., Aronson, P. S., Orlowski, J., Grinstein, S., and Alexander, R. T. (2013) Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3. PLoS One 8, e55623
49. Serrador, J. M., Vicente-Manzanares, M., Calvo, J., Barreiro, O., Montoya, M. C., Schwartz-Albiez, R., Furthmayr, H., Lozano, F., and Sánchez-Madrid, F. (2002) A novel serine-rich motif in the intercellular adhesion molecule 3 is critical for its ezrin/radixin/moesin-directed subcellular targeting. J. Biol. Chem. 277, 10400-10409 (Pubitemid 34968160)
50. Sandu, C., Artunc, F., Palmada, M., Rexhepaj, R., Grahammer, F., Hussain, A., Yun, C., Alessi, D. R., and Lang, F. (2006) Impaired intestinal NHE3 activity in the PDK1 hypomorphic mouse. Am. J. Physiol. Gastrointest. Liver Physiol. 291, G868-G876 (Pubitemid 44772013)