PMID- 10067896
OWN - NLM
STAT- MEDLINE
DCOM- 19990315
LR  - 20220309
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 397
IP  - 6721
DP  - 1999 Feb 25
TI  - Inhibition of transforming growth factor-beta/SMAD signalling by the 
      interferon-gamma/STAT pathway.
PG  - 710-3
AB  - Transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) have 
      opposite effects on diverse cellular functions, but the basis for this antagonism 
      is not known. TGF-beta signals through a receptor serine kinase that 
      phosphorylates and activates the transcription factors Smads 2 and 3, whereas the 
      IFN-gamma receptor and its associated protein tyrosine kinase Jak1 mediate 
      phosphorylation and activation of the transcription factor Stat1. Here we present 
      a basis for the integration of TGF-beta and IFN-gamma signals. IFN-gamma inhibits 
      the TGF beta-induced phosphorylation of Smad3 and its attendant events, namely, 
      the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus, 
      and the activation of TGFbeta-responsive genes. Acting through Jak1 and Stat1, 
      IFN-gamma induces the expression of Smad7, an antagonistic SMAD, which prevents 
      the interaction of Smad3 with the TGF-beta receptor. The results indicate a 
      mechanism of transmodulation between the STAT and SMAD signal-transduction 
      pathways.
FAU - Ulloa, L
AU  - Ulloa L
AD  - Cell Biology Program and Howard Hughes Medical Institute, Memorial 
      Sloan-Kettering Cancer Center, New York, New York 10021, USA.
FAU - Doody, J
AU  - Doody J
FAU - Massague, J
AU  - Massague J
LA  - eng
SI  - GENBANK/AF010193
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (SMAD7 protein, human)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad7 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/*antagonists & inhibitors/*metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interferon-gamma/*metabolism
MH  - Janus Kinase 1
MH  - Luciferases/genetics
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - STAT1 Transcription Factor
MH  - *Signal Transduction
MH  - Smad3 Protein
MH  - Smad7 Protein
MH  - Trans-Activators/*antagonists & inhibitors/*metabolism
MH  - Transforming Growth Factor beta/*antagonists & inhibitors/metabolism
EDAT- 1999/03/06 03:12
MHDA- 2001/03/23 10:01
CRDT- 1999/03/06 03:12
PHST- 1999/03/06 03:12 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/06 03:12 [entrez]
AID - 10.1038/17826 [doi]
PST - ppublish
SO  - Nature. 1999 Feb 25;397(6721):710-3. doi: 10.1038/17826.