Regulation of the renal na-hco3 cotransporter: xi. signal
transduction mechanisms underlying co2 stimulation.
Ruiz, Ofelia S., R. Brooks Robey, Yi-Yong Qiu, Long Jiang Wang, Cheng
Jin Li, Jianfei Ma, and Jose A. L. Arruda.
The University of Illinois at Chicago, College of Medicine and The
Chicago, VA Health Care System, West Side Division, Chicago,
Illinois
APStracts 6:0117F, 1999.
We have previously shown that CO2 stimulation of the renal Na-HCO3
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 CO2 stimulated NBC activity. To this end, we engineered OK
cells to express the C-terminal Src kinase (Csk), a negative
regulator of SFKs. CO2 stimulated NBC activity normally in
-galactosidase-expressing and untransfected control cells. In
contrast, Csk-expressing cells had normal baseline NBC activity which
was not stimulated by CO2. CO2 stimulation increased both total SFK
activity and specific tyrosine phosphorylation of Src. The specific
MEK1/2 inhibitor PD98059 completely inhibited the CO2 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 _classical_ MAPK pathway in mediating CO2
stimulated NBC activity in renal epithelial cells.
Received 28 January 1999; accepted in final form 8 June 1999.
APS Manuscript Number F017-9.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999