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

Erscheinungsjahr:

1999

Erschienen:

1999

Enthalten in:

Zur Gesamtaufnahme - volume:277

Enthalten in:

The American journal of physiology - 277(1999), 4 vom: 15. Okt., Seite F580-6

Sprache:

Englisch

Beteiligte Personen:

Ruiz, O S [VerfasserIn]
Robey, R B [VerfasserIn]
Qiu, Y Y [VerfasserIn]
Wang, L J [VerfasserIn]
Li, C J [VerfasserIn]
Ma, J [VerfasserIn]
Arruda, J A [VerfasserIn]

Links:

Volltext

Themen:

142M471B3J
1W306TDA6S
70563-58-5
7S5I7G3JQL
Benzoquinones
CSK Tyrosine-Protein Kinase
Carbon Dioxide
Carrier Proteins
Dexamethasone
EC 2.7.10.1
EC 2.7.10.2
EC 2.7.11.24
Enzyme Inhibitors
Glucocorticoids
Herbimycin
Journal Article
Lactams, Macrocyclic
Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Quinones
Research Support, U.S. Gov't, Non-P.H.S.
Rifabutin
Sodium-Bicarbonate Symporters
Src-Family Kinases

Anmerkungen:

Date Completed 17.11.1999

Date Revised 10.12.2019

published: Print

Citation Status MEDLINE

doi:

10.1152/ajprenal.1999.277.4.F580

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM104470321