Regulation of pdgf [beta] receptor-operated ca2+ channels by
phospholipase c-g1 in glomerular mesangial cells.
Ma, Heping, Hiroshi Matsunaga, Bing Li, Mario B. Marrero, and Brian N.
Ling.
Renal Division and The Center for Cell and Molecular Signaling,
Departments of Medicine and Pathology, Emory University School of
Medicine and Veterans Affairs Medical Center, Atlanta, Georgia
APStracts 3:0137F, 1996.
Platelet-derived growth factor (PDGF)-induced Ca2+ signaling
mechanisms were examined in cultured rat glomerular mesangial cells.
PDGF-BB stimulated the tyrosine phosphorylation of phospholipase C
(PLC)-g1, the formation of a PLC-g1/PDGF [beta] receptor membrane
complex, and the generation of intracellular 1,4,5-IP3. Preincubation
with a tyrosine kinase inhibitor (genistein) abolished these PDGF
-induced responses. Activation of 1 pS Ca2+ channels in cell-attached
patches by intrapipette PDGF-BB was also abolished by tyrosine kinase
inhibition. In the absence of PDGF-BB, channels were activated in
cell-attached patches exposed to intrapipette thapsigargin (1,4,5
-IP3-independent releaser of intracellular Ca2+ stores) and in excised
inside-out patches exposed to increasing "cytoplasmic" Ca2+
(10-8 M to 10-6 M). In cell-attached patches, channel activation by
PDGF-BB was abolished when extracellular Ca2+ was < 1 mM. In
glomerular mesangial cells: 1) PDGF-BB stimulates tyrosine
phosphorylation of PLC-g1, PDGF [beta] receptor/PLC-g1 membrane
complex formation, 1,4,5-IP3 production, and 1 pS Ca2+ channel
activity. 2) All four PDGF-induced responses are abolished by
tyrosine kinase inhibition. 3) PDGF receptor-operated Ca2+ channels
are sensitive to both intra- and extra-cellular Ca2+.
Received 14 August 1995; accepted in final form 18 July 1996.
APS Manuscript Number F268-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996