Intracellular acidosis activates c-src.
Yamaji, Yasuyoshi, Hirohiko Tsuganezawa, Orson W. Moe, and Robert J.
Alpern.
Department of Internal Medicine, The University of Texas
Southwestern Medical Center and Dallas Veterans Affairs Medical
Center, Dallas, Texas
APStracts 3:0327C, 1996.
The purpose of the present studies was to determine if acidosis
activates protein tyrosine kinase pathways. Incubation of MCT cells,
a renal proximal tubule cell line, in acid media caused increased
phosphotyrosine content of 60-70 and 120 kDa cytosolic proteins.
Media acidification induced a 2-fold increase in c-src activity that
occurred within 30 seconds. Significant activation occurred with
media pH changes as small as 0.07 pH units, accompanied by cell
acidification of 0.06 pH units. Na propionate addition, NH4Cl
prepulse, and nigericin addition, maneuvers which all decrease
intracellular pH in the absence of changes in extracellular pH,
activated c-src. Significant activation by Na propionate was seen
with cell pH changes as small as 0.07 pH units. Na orthovanadate, a
protein tyrosine phosphatase inhibitor, prevented c-src activation by
media acidification, but did not prevent protein tyrosine
phosphorylation. In summary, decreased intracellular pH activates c
-src. Acid activation of c-src represents a novel mechanism of c-src
activation that may be relevant to many cellular responses to
acidosis.
Received 24 February 1995; accepted in final form 20 September
1996.
APS Manuscript Number C104-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996