PMID- 10523304
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20161124
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 20
DP  - 1999 Oct 15
TI  - p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional
      activation induced by interferons.
PG  - 5601-8
AB  - Activation of cytosolic phospholipase A(2 )(cPLA(2)) is a prerequisite for the
      formation of the transcription factor complex interferon-stimulated gene factor 3
      (ISGF3) in response to interferon-alpha (IFN-alpha). Here we show that p38
      mitogen-activated protein kinase (MAPK), an activator of cPLA(2), is essential
      for both IFN-alpha and IFN-gamma signalling. SB203580, a specific inhibitor of
      p38, was found to inhibit ISGF3 formation but had no apparent effects on signal
      transducer and activator of transcription (STAT)1 homodimer formation. Regardless
      of this, the antiviral activities of both IFN-alpha and IFN-gamma were attenuated
      by SB203580. Treatment with either IFN led to rapid and transient activation of
      p38. Both IFNs induced STAT1 Ser727 phosphorylation, which was inhibited by
      SB203580 but not by an extracellular signal related kinase (ERK)1/2 inhibitor
      (PD98059). In an inducible 3T3-L1 clone, expression of dominant-negative p38 led 
      to defective STAT1 serine phosphorylation and diminished IFN-gamma-mediated
      protection against viral killing. Reporter activity mediated by ISGF3 or STAT1
      homodimer was diminished by SB203580 and enhanced by a constitutively active
      mutant of MKK6, the upstream activator of p38. Therefore, p38 plays a key role in
      the serine phosphorylation of STAT1 and transcriptional changes induced by both
      IFNs.
FAU - Goh, K C
AU  - Goh KC
AD  - Department of Cancer Biology/NB40, Lerner Research Institute, Cleveland Clinic
      Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
FAU - Haque, S J
AU  - Haque SJ
FAU - Williams, B R
AU  - Williams BR
LA  - eng
GR  - AI34039/AI/NIAID NIH HHS/United States
GR  - P01-CA62220/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Interferon Type I)
RN  - 0 (Pyridines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 452VLY9402 (Serine)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 6)
RN  - EC 2.7.12.2 (MAP2K6 protein, human)
RN  - EC 2.7.12.2 (Map2k6 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - *Calcium-Calmodulin-Dependent Protein Kinases
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - DNA-Binding Proteins/chemistry/genetics/*metabolism
MH  - Dimerization
MH  - Enzyme Inhibitors/pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Interferon Type I/pharmacology
MH  - Interferon-gamma/pharmacology
MH  - MAP Kinase Kinase 6
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/genetics/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Mutation
MH  - Phospholipases A/metabolism
MH  - Phosphorylation
MH  - Protein Structure, Quaternary
MH  - Pyridines/pharmacology
MH  - Recombinant Proteins
MH  - STAT1 Transcription Factor
MH  - Serine/metabolism
MH  - Trans-Activators/chemistry/genetics/*metabolism
MH  - Transcriptional Activation/drug effects
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC1171628
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 - 10.1093/emboj/18.20.5601 [doi]
PST - ppublish
SO  - EMBO J. 1999 Oct 15;18(20):5601-8. doi: 10.1093/emboj/18.20.5601.