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J Biol Chem, Vol. 274, Issue 28, 19593-19600, July 9, 1999
From the Department of Biochemistry and Molecular Biology, College
of Medicine, University of Arkansas for Medical Sciences,
Little Rock, Arkansas 72205
In this paper, we report that SB202190 alone, a
specific inhibitor of p38MAPK, induces low density
lipoprotein (LDL) receptor expression (6-8-fold) in a sterol-sensitive
manner in HepG2 cells. Consistent with this finding, selective
activation of the p38MAPK signaling pathway by expression
of MKK6b(E), a constitutive activator of p38MAPK,
significantly reduced LDL receptor promoter activity. Expression of the
p38MAPK
One-way Cross-talk between p38MAPK and
p42/44MAPK
INHIBITION OF p38MAPK INDUCES LOW DENSITY
LIPOPROTEIN RECEPTOR EXPRESSION THROUGH ACTIVATION OF THE
p42/44MAPK CASCADE
-isoform had a similar effect, whereas
expression of the p38MAPK 
II-isoform had no significant
effect on LDL receptor promoter activity.
SB202190-dependent increase in LDL receptor expression was
accompanied by induction of p42/44MAPK, and inhibition of
this pathway completely prevented SB202190-induced LDL receptor
expression, suggesting that p38MAPK negatively regulates
the p42/44MAPK cascade and the responses mediated by this
kinase. Cross-talk between these kinases appears to be one-way because
modulation of p42/44MAPK activity did not affect
p38MAPK activation by a variety of stress inducers. Taken
together, these findings reveal a hitherto unrecognized one-way
communication that exists between p38MAPK and
p42/44MAPK and provide the first evidence that through the
p42/44MAPK signaling cascade, the p38MAPK
-isoform negatively regulates LDL receptor expression, thus representing a novel mechanism of fine tuning cellular levels of
cholesterol in response to a diverse set of environmental cues.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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B. K. Law, M. E. Waltner-Law, A. J. Entingh, A. Chytil, M. E. Aakre, P. Norgaard, and H. L. Moses Salicylate-induced Growth Arrest Is Associated with Inhibition of p70s6k and Down-regulation of c-Myc, Cyclin D1, Cyclin A, and Proliferating Cell Nuclear Antigen J. Biol. Chem., December 1, 2000; 275(49): 38261 - 38267. [Abstract] [Full Text] [PDF]
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