Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts

Mark Donowitz, A. Janecki, S. Akhter, M. E. Cavet, F. Sanchez, G. Lamprecht, M. Zizak, W. L. Kwon, S. Khurana, C. H C Yun, Chung Ming Tse

Research output: Contribution to journalArticle

Abstract

NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na+-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinoses when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K′(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface blotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3-kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number.

Original languageEnglish (US)
Pages (from-to)30-42
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume915
StatePublished - 2000

Fingerprint

Fibroblasts
Cell membranes
Cyclic AMP-Dependent Protein Kinases
Epidermal Growth Factor
Protein Kinase C
Epithelial Cells
Cell Membrane
Caco-2 Cells
Receptor Protein-Tyrosine Kinases
Brushes
Microvilli
Phosphatidylinositol 3-Kinases
Ileum
Potassium-Hydrogen Antiporters
Biotinylation
Sodium-Hydrogen Antiporter
Confocal microscopy
Gallbladder
GTP-Binding Proteins
Confocal Microscopy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts. / Donowitz, Mark; Janecki, A.; Akhter, S.; Cavet, M. E.; Sanchez, F.; Lamprecht, G.; Zizak, M.; Kwon, W. L.; Khurana, S.; Yun, C. H C; Tse, Chung Ming.

In: Annals of the New York Academy of Sciences, Vol. 915, 2000, p. 30-42.

Research output: Contribution to journalArticle

Donowitz, Mark ; Janecki, A. ; Akhter, S. ; Cavet, M. E. ; Sanchez, F. ; Lamprecht, G. ; Zizak, M. ; Kwon, W. L. ; Khurana, S. ; Yun, C. H C ; Tse, Chung Ming. / Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts. In: Annals of the New York Academy of Sciences. 2000 ; Vol. 915. pp. 30-42.
@article{8a7ae538d03b4fb3a5252fada7d72ac7,
title = "Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts",
abstract = "NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na+-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinoses when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K′(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface blotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3-kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number.",
author = "Mark Donowitz and A. Janecki and S. Akhter and Cavet, {M. E.} and F. Sanchez and G. Lamprecht and M. Zizak and Kwon, {W. L.} and S. Khurana and Yun, {C. H C} and Tse, {Chung Ming}",
year = "2000",
language = "English (US)",
volume = "915",
pages = "30--42",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts

AU - Donowitz, Mark

AU - Janecki, A.

AU - Akhter, S.

AU - Cavet, M. E.

AU - Sanchez, F.

AU - Lamprecht, G.

AU - Zizak, M.

AU - Kwon, W. L.

AU - Khurana, S.

AU - Yun, C. H C

AU - Tse, Chung Ming

PY - 2000

Y1 - 2000

N2 - NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na+-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinoses when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K′(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface blotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3-kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number.

AB - NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na+-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinoses when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K′(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface blotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3-kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number.

UR - http://www.scopus.com/inward/record.url?scp=0034525593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034525593&partnerID=8YFLogxK

M3 - Article

C2 - 11193592

AN - SCOPUS:0034525593

VL - 915

SP - 30

EP - 42

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -