Inactivation of kinase cascades in mesangial cells grown on
collagen type i.
Miralem, Tiho, and Douglas M. Templeton.
Department of Laboratory Medicine and Pathobiology, University of
Toronto
APStracts 5:0129F, 1998.
Growth on collagen type I gels is known to suppress the mitogenic
responsiveness of mesangial cells. Because these cells proliferate in
some renal diseases and themselves synthesize collagen type I, we
examined the influence of growth on collagen upon several kinase
signaling cascades involved in mesangial cell proliferation.
Quiescent mesangial cells grown on collagen type I and then
stimulated with serum showed a markedly diminished induction of the
proto-oncogene c-fos, compared to their counterparts on plastic or
fibronectin. This effect was accompanied by decreased activation of
mitogen-activated (Erk family) and Ca2+/calmodulin-dependent protein
kinases. Cells on collagen showed lower basal PKC activity and
diminished levels of PKC-[alpha] and z isoforms. Global
phosphorylation of tyrosine residues was diminished on collagen, and
tyrosine phosphorylation of Erk and focal adhesion kinase in response
to serum was not detected, in contrast to cells on plastic. We
conclude that attachment of mesangial cells to collagen type I
results in a broad suppression of protein phosphorylation that is
reflected in diminished induction of the c-fos gene and probably
underlies the conversion of cultured mesangial cells to a non
-proliferative phenotype.
Received 6 January 1998; accepted in final form 22 July 1998.
APS Manuscript Number F2-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998