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Genomes and Genes | M DonowitzSummaryAffiliation: Johns Hopkins University Country: USA Publications
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SLC9/NHE gene family, a plasma membrane and organellar family of Na⁺/H⁺ exchangersMark Donowitz
Departments of Medicine and Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Mol Aspects Med 34:236-51. 2013....
Alterations in the proteome of the NHERF2 knockout mouse jejunal brush border membrane vesiclesM Donowitz
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2195, USA
Physiol Genomics 43:674-84. 2011....- Alterations in the proteome of the NHERF1 knockout mouse jejunal brush border membrane vesiclesM Donowitz
Department of Medicine, Div of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2195, USA
Physiol Genomics 42:200-10. 2010.... - NHE3 regulatory complexesMark Donowitz
Johns Hopkins University School of Medicine, 720 Rutland Avenue Baltimore, MD 21205, USA
J Exp Biol 212:1638-46. 2009..This is a review of the domain structure of NHE3 and of the scaffolding function and role in the regulation of NHE3 of the NHE3 C-terminal domain... 
Regulatory binding partners and complexes of NHE3Mark Donowitz
Department of Medicine, GI Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Physiol Rev 87:825-72. 2007..This review deals with short-term regulation of NHE3 and the identity and function of its recognized interacting partners and the multiprotein complexes in which NHE3 functions...- NHERF family and NHE3 regulationMark Donowitz
John Hopkins University School of Medicine, Departments of Medicine and Physiology, Baltimore, MD 21205, USA
J Physiol 567:3-11. 2005..In this case, NHERF2 directly binds cGKII in the brush border to form an NHE3 complex, with cGKII also associating with the BB via its myristoylation... - The attrition of young physician-scientists: problems and potential solutionsMark Donowitz
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2195, USA
Gastroenterology 132:477-80. 2007..We propose strategies that seek to address this problem and help sustain young physician-scientists at career transition points at which they are most vulnerable to give up... - Cloning and expression of a rabbit cDNA encoding a serum-activated ethylisopropylamiloride-resistant epithelial Na+/H+ exchanger isoform (NHE-2)C M Tse
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
J Biol Chem 268:11917-24. 1993..Thus, we conclude that NHE-2 is a candidate to be an apical membrane Na+/H+ exchanger in intestinal and renal epithelial cells... - Basic fibroblast growth factor stimulates surface expression and activity of Na(+)/H(+) exchanger NHE3 via mechanism involving phosphatidylinositol 3-kinaseA J Janecki
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Texas Medical School, Houston, Texas 77030, USA
J Biol Chem 275:8133-42. 2000.... - cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation of NHE regulatory factorM Zizak
Department of Medicine, Gl Division, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 274:24753-8. 1999..This study shows that members of the regulatory factor gene family, NHE-RF and E3KARP, are necessary for cAMP inhibition of NHE3 by allowing NHE3 to be phosphorylated. This inhibition is not dependent on the phosphorylation of NHE-RF... - Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblastsM Donowitz
Departments of Physiology and Medicine, Johns Hopkins University School of Medicine, 720 Ruland Avenue, Baltimore, MD 21205 2195, USA
Ann N Y Acad Sci 915:30-42. 2000.... - Half-lives of plasma membrane Na(+)/H(+) exchangers NHE1-3: plasma membrane NHE2 has a rapid rate of degradationM E Cavet
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Am J Physiol Cell Physiol 281:C2039-48. 2001..These results suggest fundamental differences in the cellular processing and trafficking of NHE2 and NHE3. These differences may underlie the specialized roles that these exchangers play in epithelial cells... - Tissue-specific regulation of sodium/proton exchanger isoform 3 activity in Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) null mice. cAMP inhibition is differentially dependent on NHERF1 and exchange protein directly activated by cAMP in ileum versus Rakhilya Murtazina
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 282:25141-51. 2007.... - Na+-H+ exchanger 3 (NHE3) is present in lipid rafts in the rabbit ileal brush border: a role for rafts in trafficking and rapid stimulation of NHE3X Li
Department of Medicine, GI Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2195, USA
J Physiol 537:537-52. 2001.... - cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory proteinC H Yun
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 94:3010-5. 1997..Transfection in PS120/NHE3 fibroblasts with either NHERF or E3KARP reconstituted cAMP-induced inhibition of NHE3, resulting in 25-30% inhibition in these cells... - Physical and genetic mapping of a human apical epithelial Na+/H+ exchanger (NHE3) isoform to chromosome 5p15.3S R Brant
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Genomics 15:668-72. 1993..Linkage analysis between NHE3 and other markers known to map at 5p15 confirmed the localization of NHE3 to chromosome 5p15.3, making NHE3 the most telomeric gene identified on the short arm of chromosome 5... - Two histidine residues in the juxta-membrane cytoplasmic domain of Na+/H+ exchanger isoform 3 (NHE3) determine the set pointB Cha
GI Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Membr Biol 191:49-58. 2003..We suggest that His-479 and His-499 are part of the H+ sensor, which is involved in determining the sensitivity to the intracellular H+ concentration and Na+/H+ exchange rate... - Constitutively active phosphatidylinositol 3-kinase and AKT are sufficient to stimulate the epithelial Na+/H+ exchanger 3W Lee-Kwon
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 276:31296-304. 2001..These results demonstrate that activation of PI 3-kinase or Akt is sufficient to stimulate NHE3 transport activity in PS120/NHE3 cells... - Na(+)/H(+) exchanger 3 is in large complexes in the center of the apical surface of proximal tubule-derived OK cellsS Akhter
Department of Medicine, Gastrointestinal Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA
Am J Physiol Cell Physiol 283:C927-40. 2002..In the BB fraction, NHE3 is largely in the detergent-insoluble fraction in lipid rafts and/or in large heterogenous complexes ranging from approximately 400 to approximately 900 kDa... - Mammalian Na+/H+ exchanger gene family: structure and function studiesC H Yun
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Am J Physiol 269:G1-11. 1995..The present review deals with the recent developments in the molecular identification of the Na+/H+ exchanger gene family, the functional characteristics, and the short-term regulation of Na+/H+ exchange at molecular and cellular levels... - Human duodenal mucosal brush border Na(+)/H(+) exchangers NHE2 and NHE3 alter net bicarbonate movementM Repishti
Department of Medicine, University of California at San Diego, San Diego, California 92103 8413, USA
Am J Physiol Gastrointest Liver Physiol 281:G159-63. 2001.... - Role of lipid rafts in Shiga toxin 1 interaction with the apical surface of Caco-2 cellsO Kovbasnjuk
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
J Cell Sci 114:4025-31. 2001..Although disruption of lipid rafts by cholesterol depletion did not affect the amount of bound Shiga toxin 1 B-subunit, lipid rafts are necessary for toxin uptake across the apical membrane of Caco-2 cells... - Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3S R Brant
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2195, USA
Am J Physiol 269:C198-206. 1995..7 kb, whereas both 6.7- and 8.9-kb bands were expressed nearly equivalently in the other tissues. No NHE3 message was detected in the human heart, lung, liver, skeletal muscle, or pancreas... - Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchangerC M Tse
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
EMBO J 10:1957-67. 1991..The near identity of the basolateral Na+/H+ exchanger and the human Na+/H+ exchanger plus the ubiquitous expression of this message suggests that the ileal basolateral Na+/H+ exchanger is the 'housekeeping' Na+/H+ exchanger... - NHERF2 is necessary for basal activity, second messenger inhibition, and LPA stimulation of NHE3 in mouse distal ileumRakhilya Murtazina
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Am J Physiol Cell Physiol 301:C126-36. 2011.... - NHERF1 and NHERF2 are necessary for multiple but usually separate aspects of basal and acute regulation of NHE3 activityRafiquel Sarker
Gastroenterology and Hepatology Division, Department of Medicine, Johns Hopkins Univ School of Medicine, Baltimore, MD 21205 2195, USA
Am J Physiol Cell Physiol 300:C771-82. 2011..cAMP-dependent inhibition of NHE3 activity requires either NHERF1 or NHERF2. Stimulation of NHE3 activity by EGF is NHERF1 dependent... - The NHE3 juxtamembrane cytoplasmic domain directly binds ezrin: dual role in NHE3 trafficking and mobility in the brush borderBoyoung Cha
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Biol Cell 17:2661-73. 2006.... - Human Na(+)/H(+) exchanger isoform 6 is found in recycling endosomes of cells, not in mitochondriaChristopher L Brett
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Am J Physiol Cell Physiol 282:C1031-41. 2002..These results suggest that, like its homologs in yeast and plants, NHE6 is an endosomal Na(+)/H(+) exchanger that may regulate intravesicular pH and volume and contribute to lysosomal biogenesis... - Cystic fibrosis transmembrane conductance regulator activation is reduced in the small intestine of Na+/H+ exchanger 3 regulatory factor 1 (NHERF-1)- but Not NHERF-2-deficient miceNellie Broere
Department of Biochemistry, Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands
J Biol Chem 282:37575-84. 2007.... - Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null miceRochelle Cunningham
Univ of Maryland School of Medicine, 22 S Greene St, N3W143, Baltimore, MD 21201, USA
Am J Physiol Renal Physiol 294:F1001-7. 2008.... - The lateral mobility of NHE3 on the apical membrane of renal epithelial OK cells is limited by the PDZ domain proteins NHERF1/2, but is dependent on an intact actin cytoskeleton as determined by FRAPBoyoung Cha
Department of Physiology, Gastroenterology Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Cell Sci 117:3353-65. 2004..05 microM, 30 minutes) reduced the NHE3 Mf (21.9+/-4.5%) without altering the Deff. Therefore the actin cytoskeleton, independently of NHERF1/2 binding, is necessary for apical membrane mobility of NHE3... - The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancerOlga Kovbasnjuk
Division of Gastroenterology, Department of Medicine, and Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 102:19087-92. 2005..These data demonstrate the appearance of a subpopulation of Gb(3) containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness... - The epithelial brush border Na+/H+ exchanger NHE3 associates with the actin cytoskeleton by binding to ezrin directly and via PDZ domain-containing Na+/H+ exchanger regulatory factor (NHERF) proteinsBoyoung Cha
Department of Medicine, GI Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Clin Exp Pharmacol Physiol 35:863-71. 2008..However, it is dynamic; for example, changing in some cases of signalling. Furthermore, NHERF binding is necessary for lysophosphatidic acid stimulation of NHE3 and inhibition of NHE3 by Ca(2+), cAMP and cGMP... - Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosisJae Ho Kim
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 277:23714-24. 2002..From these results, we propose that elevated Ca(2+) inhibits NHE3 activity through oligomerization and endocytosis of NHE3, which occurs via formation of an NHE3-E3KARP-alpha-actinin-4 complex... - Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signallingMatthew J Mahon
Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA
Nature 417:858-61. 2002.... - Lysophosphatidic acid stimulates brush border Na+/H+ exchanger 3 (NHE3) activity by increasing its exocytosis by an NHE3 kinase A regulatory protein-dependent mechanismWhaseon Lee-Kwon
Department of Physiology, Gastrointestinal Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 278:16494-501. 2003..This is the first demonstration that rapid stimulation of NHE3 activity is dependent on an apical membrane PDZ domain protein... - The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma linesSylvia Julien Grille
Developmental Genetics of Melanocytes, UMR 146 CNRS Institut Curie, 91405 Orsay Cedex, France
Cancer Res 63:2172-8. 2003..These findings suggest that future therapies based on AKT inhibition may complement conventional treatments by controlling tumor cell invasion and metastasis... - Ca2+-dependent inhibition of NHE3 requires PKC alpha which binds to E3KARP to decrease surface NHE3 containing plasma membrane complexesWhaseon Lee-Kwon
Johns Hopkins Univ School of Medicine, 925 Ross Research Bldg, 720 Rutland Ave, Baltimore, MD 21205 2195, USA
Am J Physiol Cell Physiol 285:C1527-36. 2003..These results suggest that PKCalpha is not necessary for the Ca2+-dependent formation of the NHE3 plasma membrane complex, although it is necessary for decreasing the membrane amounts of NHE3, probably by stimulating NHE3 endocytosis... - Akt2, phosphatidylinositol 3-kinase, and PTEN are in lipid rafts of intestinal cells: role in absorption and differentiationXshang Li
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Gastroenterology 126:122-35. 2004..However, how NHE3 is regulated by the PI 3-K pathway and the role of Akt2 are poorly defined... - Carbachol regulation of rabbit ileal brush border Na+-H+ exchanger 3 (NHE3) occurs through changes in NHE3 trafficking and complex formation and is Src dependentXuhang Li
Department of Medicine, GI Division, John Hopkins University School of Medicine, Baltimore, MD 21205-2195, USA
J Physiol 556:791-804. 2004.... - NHERF2 increases platelet-derived growth factor-induced proliferation through PI-3-kinase/Akt-, ERK-, and Src family kinase-dependent pathwayYong Jung Kang
Department of Physiology, College of Medicine, Pusan National University, 1Ga, Ami dong, Suh gu, Pusan 602 739, South Korea
Cell Signal 16:791-800. 2004..These results suggest that NHERF2 stimulates PDGF-induced proliferation by increasing PI-3-kinase/Akt, MEKindependent ERK, and Src family kinase-mediated signaling pathways... - Molecular physiology of intestinal Na+/H+ exchangeNicholas C Zachos
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2195, USA
Annu Rev Physiol 67:411-43. 2005.... - cGMP inhibition of Na+/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring proteinBoyoung Cha
Department of Physiology, GI Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 280:16642-50. 2005..These results show that NHERF2, acting as a novel protein kinase G-anchoring protein, is required for cGMP inhibition of NHE3 and that cGKII must be bound both to the plasma membrane by its myristoyl anchor and to NHERF2 to inhibit NHE3... - Lysophosphatidic acid induces exocytic trafficking of Na(+)/H(+) exchanger 3 by E3KARP-dependent activation of phospholipase CJung Woong Choi
Department of Physiology and Medicine, Gastrointestinal Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Biochim Biophys Acta 1683:59-68. 2004.... - Evolutionary origins of eukaryotic sodium/proton exchangersChristopher L Brett
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Am J Physiol Cell Physiol 288:C223-39. 2005..These novel observations have allowed us to use comparative biology to predict physiological roles for the nine human NHE paralogs and to propose appropriate model organisms in which to study the unique properties of each NHE subclass... - Does the proteome encode organellar pH?Christopher L Brett
Department of Physiology, The Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA
FEBS Lett 580:717-9. 2006..This raises an interesting evolutionary question: did the pI of proteins and the pH of organelles co-evolve to optimize function?.. - Na+/H+ exchanger NHE3 activity and trafficking are lipid Raft-dependentRakhilya Murtazina
Departments of Physiology and Medicine, Division of Gastroenterology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
J Biol Chem 281:17845-55. 2006.... - Proteome of murine jejunal brush border membrane vesiclesMark Donowitz
J Proteome Res 6:4068-79. 2007..This study helps to further define the brush border membrane vesicle, a preparation which has been widely used to identify transport function of the small intestine... - Fractionation of subcellular membrane vesicles of epithelial and nonepithelial cells by OptiPrep density gradient ultracentrifugationXuhang Li
GI Division, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Methods Mol Biol 440:97-110. 2008.... - Latrunculin B facilitates Shiga toxin 1 transcellular transcytosis across T84 intestinal epithelial cellsIrina Maluykova
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Biochim Biophys Acta 1782:370-7. 2008..Since EHEC attachment to epithelial cells causes an actin rearrangement, this finding may be highly relevant to Stx-induced disease... - ClC-5: role in endocytosis in the proximal tubuleYingHong Wang
Dept of Physiology, WBSB Rm 208, The Johns Hopkins Univ School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
Am J Physiol Renal Physiol 289:F850-62. 2005..Our data from the mutants suggest that defective targeting and trafficking of mutant ClC-5 to the endosomes are a major determinant in the lack of normal endocytosis in Dent's disease...
Research Grants
- Diarrheal Disease -- A Physiologic Approach to TreatmentMark Donowitz; Fiscal Year: 2007..We also will test effects of stimulation of NHE3 on its BB mobility by use of fluorescence recovery after photobleaching (FRAP). ..
- PDZ Domain Proteins and NHE3 RegulationMark Donowitz; Fiscal Year: 2007..abstract_text> ..
- Hopkins Digestive Diseases Basic Research Development CenterMark Donowitz; Fiscal Year: 2007..Administrative Operations will provide the communication, financial management and administrative functions of the DDBRDC. ..
- BASIC SCIENCE RESEARCH IN DIGESTIVE DISEASEMark Donowitz; Fiscal Year: 2007..Fellows who are thought to be successful in being prepared for investigative careers are helped to obtain bridging support and brought on as junior faculty to allow adequate time for training. ..
- Diarrheal Disease: A Physiologic Approach to TreatmentMark Donowitz; Fiscal Year: 2009..In addition, the coordinated association with NHE3 of these proteins which all bind to a small area of NHE3, will be examined to determine if together they explain how NHE3 changes its activity during digestion and in diarrhea. ..
- Diarrheal Disease: A Physiologic Approach to TreatmentMark Donowitz; Fiscal Year: 2010..In addition, the coordinated association with NHE3 of these proteins which all bind to a small area of NHE3, will be examined to determine if together they explain how NHE3 changes its activity during digestion and in diarrhea. ..
- NHE3 Regulation and Signaling ComplexesChung Ming Tse; Fiscal Year: 2010..We suspect that this will provide insight in how normal Na absorption occurs as well as how Na absorption becomes abnormal in diarrheal diseases. ..
- Diarrheal Disease: A Physiologic Approach to TreatmentMark Donowitz; Fiscal Year: 2009..In addition, the coordinated association with NHE3 of these proteins which all bind to a small area of NHE3, will be examined to determine if together they explain how NHE3 changes its activity during digestion and in diarrhea. ..
- NHE3 Regulation and Signaling ComplexesMark Donowitz; Fiscal Year: 2009..We suspect that this will provide insight in how normal Na absorption occurs as well as how Na absorption becomes abnormal in diarrheal diseases. ..
- DIARRHEAL DISEASE--A PHYSIOLOGIC APPROACH TO TREATMENTMark Donowitz; Fiscal Year: 1993..II. To direct the biochemical studies in I, the identity of the ileal brush border PL(s) activated by carbachol and/or A23187 and the mechanism of their activation will probed...
- DIARRHEAL DISEASE: A PHYSIOLOGIC APPROACH TO TREATMENTMark Donowitz; Fiscal Year: 1990....
- DIARRHEAL DISEASE--A PHYSIOLOGIC APPROACH TO TREATMENTMark Donowitz; Fiscal Year: 1992....
- DIARRHEAL DISEASE--A PHYSIOLOGIC APPROACH TO TREATMENTMark Donowitz; Fiscal Year: 2002....
- Diarrheal Disease: A Physiologic Approach to TreatmentMark Donowitz; Fiscal Year: 2010..In addition, the coordinated association with NHE3 of these proteins which all bind to a small area of NHE3, will be examined to determine if together they explain how NHE3 changes its activity during digestion and in diarrhea. ..