PMID- 10446219
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 34
DP  - 1999 Aug 20
TI  - Protein kinase C delta associates with and phosphorylates Stat3 in an
      interleukin-6-dependent manner.
PG  - 24392-400
AB  - Stat3 is activated by phosphorylation on Tyr-705, which leads to dimer formation,
      nuclear translocation, and regulation of gene expression. Serine phosphorylation 
      of Stat3 by mitogen-activated protein kinase has also been observed in cells
      responding to epidermal growth factor and shown to affect its tyrosine
      phosphorylation and transcriptional activity. Serine phosphorylation of Stat3 is 
      also induced by interleukin-6 (IL-6) stimulation, which is shown to be
      independent of mitogen-activated protein kinase and sensitive to the Ser/Thr
      kinase inhibitor H7. In this study, we investigated whether protein kinase C
      (PKC) is the kinase that is induced and responsible for Stat3 serine
      phosphorylation by IL-6 stimulation and which isoform of PKCs is likely to be
      involved. Here, we report that Stat3 was specifically associated with PKC delta
      in vivo in an IL-6-dependent manner in several cell types. Furthermore, Stat3 was
      phosphorylated by PKC delta in vivo on Ser-727, which could be inhibited either
      by a specific PKC delta inhibitor or by a dominant-negative mutant of PKC delta. 
      Finally, we showed that the phosphorylation of Stat3 by PKC delta led to a
      negative regulation of Stat3 DNA binding and transcriptional activity. These
      results indicate that PKC delta is likely to be the kinase that phosphorylates
      Stat3 in response to IL-6 stimulation and suggest a possible regulatory role of
      PKC delta on Stat3 function.
FAU - Jain, N
AU  - Jain N
AD  - Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National
      University of Singapore, 30 Medical Dr., Singapore 117609.
FAU - Zhang, T
AU  - Zhang T
FAU - Kee, W H
AU  - Kee WH
FAU - Li, W
AU  - Li W
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 (Interleukin-6)
RN  - 0 (Isoenzymes)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 452VLY9402 (Serine)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/physiology
MH  - Cell Line
MH  - DNA/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Epidermal Growth Factor/pharmacology
MH  - Humans
MH  - Interleukin-6/*pharmacology
MH  - Isoenzymes/*physiology
MH  - Mitogen-Activated Protein Kinase 1
MH  - Phosphorylation
MH  - Protein Kinase C/*physiology
MH  - STAT3 Transcription Factor
MH  - Serine/metabolism
MH  - Trans-Activators/*metabolism
MH  - Transcriptional Activation
EDAT- 1999/08/14 00:00
MHDA- 1999/08/14 00:01
CRDT- 1999/08/14 00:00
PHST- 1999/08/14 00:00 [pubmed]
PHST- 1999/08/14 00:01 [medline]
PHST- 1999/08/14 00:00 [entrez]
AID - 10.1074/jbc.274.34.24392 [doi]
AID - S0021-9258(19)55572-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 20;274(34):24392-400. doi: 10.1074/jbc.274.34.24392.