PubMed Journals: J Biol Chem
Source: PMID: 10521505
⇦ ⇨ J Biol Chem. 1999 Oct 22;274(43):31055-61.
Serine phosphorylation and negative regulation
of Stat3 by JNK.
Lim CP(1), Cao X.
(1) Signal Transduction Laboratory, Institute
of Molecular and Cell Biology, National
University of Singapore, Singapore 117609.
STATs are activated by various cytokines and
growth factors via tyrosine phosphorylation,
which leads to sequential dimer formation,
nuclear translocation, binding to specific
DNA sequences, and regulation of gene expression.
Recently, serine phosphorylation of Stat3
on Ser-727 by ERK has been identified in
response to epidermal growth factor (EGF).
Here, we report that Ser-727 phosphorylation
of Stat3 can also be induced by JNK and
activated either by stress or by its upstream
kinase and that various stress treatments
induce serine phosphorylation of Stat3 in
the absence of tyrosine phosphorylation.
Inhibitors of ERK and p38 did not inhibit
UV-induced Stat3 serine phosphorylation,
suggesting that neither of them is involved.
We further demonstrate that JNK1, activated
by its upstream kinase MKK7, negatively
regulated the tyrosine phosphorylation and
DNA binding and transcriptional activities
of Stat3 stimulated by EGF. Correspondingly,
pretreatment of cells with UV reduced the
EGF-stimulated tyrosine phosphorylation
and phosphotyrosine-dependent activities
of Stat3. The inhibitory effect was not
observed for Stat1. Our results suggest
that Stat3 is a target of JNK that may regulate
Stat3 activity via both Ser-727
phosphorylation-dependent and -independent
PMID: 10521505 [Indexed for MEDLINE]