The peptide transporter PEPT2 is targeted by the protein kinase SGK1 and the scaffold protein NHERF2

Cellular Physiology and Biochemistry

Volumn 22, Issue 5-6, 2008, Pages 705-714

  Boehmer, Christoph ^a,b   Palmada, Monica ^a,b   Klaus, Fabian ^a   Jeyaraj, Sankarganesh ^a   Lindner, Ricco ^a   Laufer, Jörg ^a   Daniel, Hannelore ^c   Lang, Florian ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b UNIVERSITY OF DUISBURG ESSEN   (Germany)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Peptide; Phosphorylation; Signal transduction; Tansporter; Transport

Indexed keywords

PEPTIDE TRANSPORTER 2; SERINE; SERUM AND GLUCOCORTICOID REGULATED KINASE 1; SODIUM PROTON EXCHANGE PROTEIN 2;

ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL SURFACE; CONTROLLED STUDY; ELECTROPHYSIOLOGY; FEMALE; GENE DELETION; IMMUNOASSAY; NONHUMAN; OOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; PROTEIN TRANSPORT; TRANSLATION REGULATION; XENOPUS;

EID: 57649199838     PISSN: 10158987     EISSN: None     Source Type: Journal    
DOI: 10.1159/000185554     Document Type: Article

References (76)

1. Daniel H: Molecular and integrative physiology of intestinal peptide transport. Annu Rev Physiol 2004;66:361-384.
2. Daniel H, Kottra G: The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch 2004;447:610-618.
3. Meredith D, Boyd CA: Structure and function of eukaryotic peptide transporters. Cell Mol Life Sci 2000;57:754-778.
4. Daniel H, Herget M: Cellular and molecular mechanisms of renal peptide transport. Am J Physiol 1997;273:F1-F8.
5. Boll M, Markovich D, Weber WM, Korte H, Daniel H, Murer H: Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, beta-lactam antibiotics and ACE-inhibitors. Pflugers Arch 1994;429:146-149.
6. Boll M, Herget M, Wagener M, Weber WM, Markovich D, Biber J, Clauss W, Murer H, Daniel H: Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc Natl Acad Sci U S A 1996;93:284-289.
7. Fei YJ, Kanai Y, Nussberger S, Ganapathy V, Leibach FH, Romero MF, Singh SK, Boron WF, Hediger MA: Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 1994;368:563-566.
8. Bockman DE, Ganapathy V, Oblak TG, Leibach FH: Localization of peptide transporter in nuclei and lysosomes of the pancreas. Int J Pancreatol 1997;22:221-225.
9. Knutter I, Rubio-Aliaga I, Boll M, Hause G, Daniel H, Neubert K, Brandsch M: H+-peptide cotransport in the human bile duct epithelium cell line SK-ChA-1. Am J Physiol Gastrointest Liver Physiol 2002;283:G222-G229.
10. Berger UV, Hediger MA: Distribution of peptide transporter PEPT2 mRNA in the rat nervous system. Anat Embryol (Berl) 1999;199:439-449.
11. Groneberg DA, Nickolaus M, Springer J, Doring F, Daniel H, Fischer A: Localization of the peptide transporter PEPT2 in the lung: implications for pulmonary oligopeptide uptake. Am J Pathol 2001;158:707-714.
12. Groneberg DA, Doring F, Theis S, Nickolaus M, Fischer A, Daniel H: Peptide transport in the mammary gland: expression and distribution of PEPT2 mRNA and protein. Am J Physiol Endocrinol Metab 2002;282:E1172-E1179.
13. Ihara T, Tsujikawa T, Fujiyama Y, Bamba T: Regulation of PepT1 peptide transporter expression in the rat small intestine under malnourished conditions. Digestion 2000;61:59-67.
14. Pan X, Terada T, Irie M, Saito H, Inui K: Diurnal rhythm of H+-peptide cotransporter in rat small intestine. Am J Physiol Gastrointest Liver Physiol 2002;283:G57-G64.
15. Thamotharan M, Bawani SZ, Zhou X, Adibi SA: Functional and molecular expression of intestinal oligopeptide transporter (Pept-1) after a brief fast. Metabolism 1999;48:681-684.
16. Ziegler TR, Fernandez-Estivariz C, Gu LH, Bazargan N, Umeakunne K, Wallace TM, Diaz EE, Rosado KE, Pascal RR, Galloway JR, Wilcox JN, Leader LM: Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome. Am J Clin Nutr 2002;75:922-930.
17. Ashida K, Katsura T, Motohashi H, Saito H, Inui K: Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol 2002;282:G617-G623.
18. Takahashi K, Masuda S, Nakamura N, Saito H, Futami T, Doi T, Inui K: Upregulation of H(+)-peptide cotransporter PEPT2 in rat remnant kidney. Am J Physiol Renal Physiol 2001;281:F1109-F1116.
19. Brandsch M, Miyamoto Y, Ganapathy V, Leibach FH: Expression and protein kinase C-dependent regulation of peptide/H+ co-transport system in the Caco-2 human colon carcinoma cell line. Biochem J 1994;299 ( Pt 1):253-260.
20. Wenzel U, Diehl D, Herget M, Kuntz S, Daniel H: Regulation of the high-affinity H+/peptide cotransporter in renal LLC-PK1 cells. J Cell Physiol 1999;178:341-348.
21. Park J, Leong ML, Buse P, Maiyar AC, Firestone GL, Hemmings BA: Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J 1999;18:3024-3033.
22. Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V: (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol Rev 2006;86:1151-1178.
23. Fanning AS, Anderson JM: PDZ domains: fundamental building blocks in the organization of protein complexes at the plasma membrane. J Clin Invest 1999;103:767-772.
24. Hall RA, Ostedgaard LS, Premont RT, Blitzer JT, Rahman N, Welsh MJ, Lefkowitz RJ: A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. Proc Natl Acad Sci U S A 1998;95:8496-8501.
25. Schneider S, Buchert M, Georgiev O, Catimel B, Halford M, Stacker SA, Baechi T, Moelling K, Hovens CM: Mutagenesis and selection of PDZ domains that bind new protein targets. Nat Biotechnol 1999;17:170-175.
26. Songyang Z, Fanning AS, Fu C, Xu J, Marfatia SM, Chishti AH, Crompton A, Chan AC, Anderson JM, Cantley LC: Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 1997;275:73-77.
27. Stricker NL, Christopherson KS, Yi BA, Schatz PJ, Raab RW, Dawes G, Bassett DE, Jr., Bredt DS, Li M: PDZ domain of neuronal nitric oxide synthase recognizes novel C-terminal peptide sequences. Nat Biotechnol 1997;15:336-342.
28. Fanning AS, Anderson JM: Protein modules as organizers of membrane structure. Curr Opin Cell Biol 1999;11:432-439.
29. Garner CC, Nash J, Huganir RL: PDZ domains in synapse assembly and signalling. Trends Cell Biol 2000;10:274-280.
30. Hung AY, Sheng M: PDZ domains: structural modules for protein complex assembly. J Biol Chem 2002;277:5699-5702.
31. Ogura T, Furukawa T, Toyozaki T, Yamada K, Zheng YJ, Katayama Y, Nakaya H, Inagaki N: ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC. FASEB J 2002;16:863-865.
32. Tang Y, Tang J, Chen Z, Trost C, Flockerzi V, Li M, Ramesh V, Zhu MX: Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J Biol Chem 2000;275:37559-37564.
33. Wang S, Raab RW, Schatz PJ, Guggino WB, Li M: Peptide binding consensus of the NHE-RF-PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane conductance regulator (CFTR). FEBS Lett 1998;427:103-108.
34. Weinman EJ, Wang Y, Wang F, Greer C, Steplock D, Shenolikar S: A C-terminal PDZ motif in NHE3 binds NHERF-1 and enhances cAMP inhibition of sodium-hydrogen exchange. Biochemistry 2003;42:12662-12668.
35. Weinman EJ, Steplock D, Shenolikar S: NHERF-1 uniquely transduces the cAMP signals that inhibit sodium-hydrogen exchange in mouse renal apical membranes. FEBS Lett 2003;536:141-144.
36. Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M: cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A 1997;94:3010-3015.
37. Weinman EJ, Minkoff C, Shenolikar S: Signal complex regulation of renal transport proteins: NHERF and regulation of NHE3 by PKA. Am J Physiol Renal Physiol 2000;279:F393-F399.
38. Weinman EJ, Steplock D, Donowitz M, Shenolikar S: NHERF associations with sodium-hydrogen exchanger isoform 3 (NHE3) and ezrin are essential for cAMP-mediated phosphorylation and inhibition of NHE3. Biochemistry 2000;39:6123-6129.
39. Embark HM, Setiawan I, Poppendieck S, van de Graaf SF, Boehmer C, Palmada M, Wieder T, Gerstberger R, Cohen P, Yun CC, Bindels RJ, Lang F: Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Cell Physiol Biochem 2004;14:203-212.
40. Palmada M, Poppendieck S, Embark HM, van de Graaf SF, Boehmer C, Bindels RJ, Lang F: Requirement of PDZ domains for the stimulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase SGK1. Cell Physiol Biochem 2005;15:175-182.
41. Yun CC, Palmada M, Embark HM, Fedorenko O, Feng Y, Henke G, Setiawan I, Boehmer C, Weinman EJ, Sandrasagra S, Korbmacher C, Cohen P, Pearce D, Lang F: The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1. J Am Soc Nephrol 2002;13:2823-2830.
42. Wade JB, Liu J, Coleman RA, Cunningham R, Steplock DA, Lee-Kwon W, Pallone TL, Shenolikar S, Weinman EJ: Localization and interaction of NHERF isoforms in the renal proximal tubule of the mouse. Am J Physiol Cell Physiol 2003;285:C1494-C1503.
43. Weinman EJ, Lakkis J, Akom M, Wali RK, Drachenberg CB, Coleman RA, Wade JB: Expression of NHERF-1, NHERF-2, PDGFR-alpha, and PDGFR-beta in normal human kidneys and in renal transplant rejection. Pathobiology 2002;70:314-323.
44. Kobayashi T, Cohen P: Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem J 1999;339 ( Pt 2):319-328.
45. Wagner CA, Friedrich B, Setiawan I, Lang F, Broer S: The use of Xenopus laevis oocytes for the functional characterization of heterologously expressed membrane proteins. Cell Physiol Biochem 2000;10:1-12.
46. Bagowski CP, Myers JW, Ferrell JE, Jr.: The classical progesterone receptor associates with p42 MAPK and is involved in phosphatidylinositol 3-kinase signaling in Xenopus oocytes. J Biol Chem 2001;276:37708-37714.
47. Hillier BJ, Christopherson KS, Prehoda KE, Bredt DS, Lim WA: Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science 1999;284:812-815.
48. van Huizen R, Miller K, Chen DM, Li Y, Lai ZC, Raab RW, Stark WS, Shortridge RD, Li M: Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling. EMBO J 1998;17:2285-2297.
49. Xu XZ, Choudhury A, Li X, Montell C: Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins. J Cell Biol 1998;142:545-555.
50. Boehmer C, Henke G, Schniepp R, Palmada M, Rothstein JD, Broer S, Lang F: Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. J Neurochem 2003;86:1181-1188.
51. Boehmer C, Embark HM, Bauer A, Palmada M, Yun CH, Weinman EJ, Endou H, Cohen P, Lahme S, Bichler KH, Lang F: Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B. Biochem Biophys Res Commun 2004;313:998-1003.
52. Boehmer C, Rajamanickam J, Schniepp R, Kohler K, Wulff P, Kuhl D, Palmada M, Lang F: Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochem Biophys Res Commun 2005;329:738-742.
53. C. Boehmer, M. Palmada, J. Rajamanickam, R. Schniepp, S. G. Amara and F. Lang. Post-translational regulation of EAAT2 function by co-expressed ubiquitin ligase Nedd4-2 is impacted by SGK kinases. 2006. Ref Type: Thesis/ Dissertation
54. Bohmer C, Philippin M, Rajamanickam J, Mack A, Broer S, Palmada M, Lang F: Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and PKB. Biochem Biophys Res Commun 2004;324:1242-1248.
55. Yun CC, Chen Y, Lang F: Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. J Biol Chem 2002;277:7676-7683.
56. Wada M, Miyakawa S, Shimada A, Okada N, Yamamoto A, Fujita T: Functional linkage of H+/peptide transporter PEPT2 and Na+/H+ exchanger in primary cultures of astrocytes from mouse cerebral cortex. Brain Res 2005;1044:33-41.
57. McCormick JA, Bhalla V, Pao AC, Pearce D: SGK1: a rapid aldosterone-induced regulator of renal sodium reabsorption. Physiology (Bethesda ) 2005;20:134-139.
58. Smith DE, Pavlova A, Berger UV, Hediger MA, Yang T, Huang YG, Schnermann JB: Tubular localization and tissue distribution of peptide transporters in rat kidney. Pharm Res 1998;15:1244-1249.
59. Kobayashi T, Deak M, Morrice N, Cohen P: Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J 1999;344 Pt 1:189-197.
60. Shenolikar S, Voltz JW, Cunningham R, Weinman EJ: Regulation of ion transport by the NHERF family of PDZ proteins. Physiology (Bethesda ) 2004;19:362-369.
61. Lamprecht G, Heil A, Baisch S, Lin-Wu E, Yun CC, Kalbacher H, Gregor M, Seidler U: The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/. Biochemistry 2002;41:12336-12342.
62. Liedtke CM, Yun CH, Kyle N, Wang D: Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor. J Biol Chem 2002;277:22925-22933.
63. Poulat F, Barbara PS, Desclozeaux M, Soullier S, Moniot B, Bonneaud N, Boizet B, Berta P: The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains. J Biol Chem 1997;272:7167-7172.
64. Sitaraman SV, Wang L, Wong M, Bruewer M, Hobert M, Yun CH, Merlin D, Madara JL: The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation. J Biol Chem 2002;277:33188-33195.
65. Wu MS, Biemesderfer D, Giebisch G, Aronson PS: Role of NHE3 in mediating renal brush border Na+-H+ exchange. Adaptation to metabolic acidosis. J Biol Chem 1996;271:32749-32752.
66. Sun F, Hug MJ, Lewarchik CM, Yun CH, Bradbury NA, Frizzell RA: E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells. J Biol Chem 2000;275:29539-29546.
67. Sun F, Hug MJ, Bradbury NA, Frizzell RA: Protein kinase A associates with cystic fibrosis transmembrane conductance regulator via an interaction with ezrin. J Biol Chem 2000;275:14360-14366.
68. Yoo D, Kim BY, Campo C, Nance L, King A, Maouyo D, Welling PA: Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A. J Biol Chem 2003;278:23066-23075.
69. Noshiro R, Anzai N, Sakata T, Miyazaki H, Terada T, Shin HJ, He X, Miura D, Inui K, Kanai Y, Endou H: The PDZ domain protein PDZK1 interacts with human peptide transporter PEPT2 and enhances its transport activity. Kidney Int 2006;70:275-282.
70. Donowitz M, Cha B, Zachos NC, Brett CL, Sharma A, Tse CM, Li X: NHERF family and NHE3 regulation. J Physiol 2005;567:3-11.
71. Frey IM, Rubio-Aliaga I, Siewert A, Sailer D, Drobyshev A, Beckers J, de Angelis MH, Aubert J, Bar HA, Fiehn O, Eichinger HM, Daniel H: Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue of Pept2-/- mice. Physiol Genomics 2007;28:301-310.
72. Rubio-Aliaga I, Frey I, Boll M, Groneberg DA, Eichinger HM, Balling R, Daniel H: Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney. Mol Cell Biol 2003;23:3247-3252.
73. Shen H, Ocheltree SM, Hu Y, Keep RF, Smith DE: Impact of genetic knockout of PEPT2 on cefadroxil pharmacokinetics, renal tubular reabsorption, and brain penetration in mice. Drug Metab Dispos 2007;35:1209-1216.
74. Busjahn A, Aydin A, Uhlmann R, Krasko C, Bahring S, Szelestei T, Feng Y, Dahm S, Sharma AM, Luft FC, Lang F: Serum- and glucocorticoid-regulated kinase (SGK1) gene and blood pressure. Hypertension 2002;40:256-260.
75. Dieter M, Palmada M, Rajamanickam J, Aydin A, Busjahn A, Boehmer C, Luft FC, Lang F: Regulation of glucose transporter SGLT1 by ubiquitin ligase Nedd4-2 and kinases SGK1, SGK3, and PKB. Obes Res 2004;12:862-870.
76. von Wowern F, Berglund G, Carlson J, Mansson H, Hedblad B, Melander O: Genetic variance of SGK-1 is associated with blood pressure, blood pressure change over time and strength of the insulin-diastolic blood pressure relationship. Kidney Int 2005;68:2164-2172.