PMID- 10521505
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 43
DP  - 1999 Oct 22
TI  - Serine phosphorylation and negative regulation of Stat3 by JNK.
PG  - 31055-61
AB  - 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 mechanisms.
FAU - Lim, C P
AU  - Lim CP
AD  - Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National
      University of Singapore, Singapore 117609.
FAU - Cao, X
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 17885-08-4 (Phosphoserine)
RN  - 452VLY9402 (Serine)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - COS Cells
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation/*physiology/radiation effects
MH  - Imidazoles/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Point Mutation
MH  - Pyridines/pharmacology
MH  - Recombinant Fusion Proteins/metabolism
MH  - STAT3 Transcription Factor
MH  - *Serine
MH  - Signal Transduction/drug effects/physiology
MH  - Trans-Activators/*metabolism
MH  - Transfection
MH  - Ultraviolet Rays
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1074/jbc.274.43.31055 [doi]
AID - S0021-9258(19)51785-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 22;274(43):31055-61. doi: 10.1074/jbc.274.43.31055.