Regulation of the renal Na-HCO(3) cotransporter. XI. Signal transduction underlying CO(2) stimulation
We have previously shown that CO(2) stimulation of the renal Na-HCO(3) cotransporter (NBC) activity is abrogated by general inhibitors of protein tyrosine kinases. The more selective inhibitor herbimycin also blocked this effect at concentrations known to preferentially inhibit Src family kinases (SFKs). We therefore examined a role for SFKs in CO(2)-stimulated NBC activity. To this end, we engineered OK cells to express the COOH-terminal Src kinase (Csk), a negative regulator of SFKs. CO(2) stimulated NBC activity normally in beta-galactosidase-expressing and untransfected control cells. In contrast, Csk-expressing cells had normal baseline NBC activity that was not stimulated by CO(2). CO(2) stimulation increased both total SFK activity and specific tyrosine phosphorylation of Src. The specific MEK1/2 inhibitor PD-98059 completely inhibited the CO(2) stimulation of NBC activity as well as the accompanying phosphorylation and activation of ERK1/2. Our data suggest the involvement of both SFKs, probably Src, and the "classic" MAPK pathway in mediating CO(2)-stimulated NBC activity in renal epithelial cells.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
1999 |
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Erschienen: |
1999 |
Enthalten in: |
Zur Gesamtaufnahme - volume:277 |
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Enthalten in: |
The American journal of physiology - 277(1999), 4 vom: 15. Okt., Seite F580-6 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Ruiz, O S [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 17.11.1999 Date Revised 10.12.2019 published: Print Citation Status MEDLINE |
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doi: |
10.1152/ajprenal.1999.277.4.F580 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM104470321 |
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100 | 1 | |a Ruiz, O S |e verfasserin |4 aut | |
245 | 1 | 0 | |a Regulation of the renal Na-HCO(3) cotransporter. XI. Signal transduction underlying CO(2) stimulation |
264 | 1 | |c 1999 | |
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520 | |a We have previously shown that CO(2) stimulation of the renal Na-HCO(3) cotransporter (NBC) activity is abrogated by general inhibitors of protein tyrosine kinases. The more selective inhibitor herbimycin also blocked this effect at concentrations known to preferentially inhibit Src family kinases (SFKs). We therefore examined a role for SFKs in CO(2)-stimulated NBC activity. To this end, we engineered OK cells to express the COOH-terminal Src kinase (Csk), a negative regulator of SFKs. CO(2) stimulated NBC activity normally in beta-galactosidase-expressing and untransfected control cells. In contrast, Csk-expressing cells had normal baseline NBC activity that was not stimulated by CO(2). CO(2) stimulation increased both total SFK activity and specific tyrosine phosphorylation of Src. The specific MEK1/2 inhibitor PD-98059 completely inhibited the CO(2) stimulation of NBC activity as well as the accompanying phosphorylation and activation of ERK1/2. Our data suggest the involvement of both SFKs, probably Src, and the "classic" MAPK pathway in mediating CO(2)-stimulated NBC activity in renal epithelial cells | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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650 | 7 | |a Carrier Proteins |2 NLM | |
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650 | 7 | |a Lactams, Macrocyclic |2 NLM | |
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700 | 1 | |a Li, C J |e verfasserin |4 aut | |
700 | 1 | |a Ma, J |e verfasserin |4 aut | |
700 | 1 | |a Arruda, J A |e verfasserin |4 aut | |
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