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J. Biol. Chem., Vol. 276, Issue 18, 14572-14580, May 4, 2001
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From UVA exposure plays an important role in the
etiology of skin cancer. The family of p90-kDa ribosomal S6 kinases
(p90RSK/MAPKAP-K1) are activated via phosphorylation. In
this study, results show that UVA-induced phosphorylation of
p90RSK at Ser381 through ERKs and JNKs, but not
p38 kinase pathways. We provide evidence that UVA-induced
p90RSK phosphorylation and kinase activity were time- and
dose-dependent. Both PD98059 and a dominant negative mutant
of ERK2 blocked ERKs and p90RSK Ser381
phosphorylation, as well as p90RSK activity. A dominant
negative mutant of p38 kinase blocked UVA-induced phosphorylation of
p38 kinase, but had no effect on UVA-induced Ser381
phosphorylation of p90RSK or kinase activity. UVA-induced
p90RSK phosphorylation and kinase activity were markedly
attenuated in JnK1
UVA Induces Ser381 Phosphorylation of
p90RSK/MAPKAP-K1 via ERK and JNK Pathways*
,
,
,
, and
¶
The Hormel Institute, University of Minnesota,
Austin, Minnesota 55912 and the § Department of
Pathophysiology, Henan Medical University,
Zhengzhou 450052, Peoples Republic of China
/
and
JnK2
/
cells. A dominant negative
mutant of JNK1 inhibited UVA-induced JNKs and
p90RSK phosphorylation and kinase activity, but had no
effect on ERKs phosphorylation. PD169316, a novel inhibitor of JNKs and
p38 kinase, inhibited phosphorylation of p90RSK, JNKs, and
p38 kinase, but not ERKs. However, SB202190, a selective inhibitor of
p38 kinase, had no effect on p90RSK or JNKs
phosphorylation. Significantly, ERKs and JNKs, but not p38 kinase,
immunoprecipitated with p90RSK when stimulated by UVA and
p90RSK was a substrate for ERK2 and JNK2, but not p38
kinase. These data indicate clearly that p90RSK
Ser381 may be phosphorylated by activation of JNKs or ERKs,
but not p38 kinase.
*
This work was supported by The Hormel Foundation and
National Institutes of Health Grants CA77646 and CA81064.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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