PMID- 10085140
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 13
DP  - 1999 Mar 26
TI  - ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth
      factor-beta signaling.
PG  - 8949-57
AB  - Upon transforming growth factor-beta (TGF-beta) binding to its cognate receptor, 
      Smad3 and Smad4 form heterodimers and transduce the TGF-beta signal to the
      nucleus. In addition to the Smad pathway, another pathway involving a member of
      the mitogen-activated protein kinase kinase kinase family of kinases,
      TGF-beta-activated kinase-1 (TAK1), is required for TGF-beta signaling. However, 
      it is unknown how these pathways function together to synergistically amplify
      TGF-beta signaling. Here we report that the transcription factor ATF-2 (also
      called CRE-BP1) is bound by a hetero-oligomer of Smad3 and Smad4 upon TGF-beta
      stimulation. ATF-2 is one member of the ATF/CREB family that binds to the cAMP
      response element, and its activity is enhanced after phosphorylation by
      stress-activated protein kinases such as c-Jun N-terminal kinase and p38. The
      binding between ATF-2 and Smad3/4 is mediated via the MH1 region of the Smad
      proteins and the basic leucine zipper region of ATF-2. TGF-beta signaling also
      induces the phosphorylation of ATF-2 via TAK1 and p38. Both of these actions are 
      shown to be responsible for the synergistic stimulation of ATF-2 trans-activating
      capacity. These results indicate that ATF-2 plays a central role in TGF-beta
      signaling by acting as a common nuclear target of both Smad and TAK1 pathways.
FAU - Sano, Y
AU  - Sano Y
AD  - Laboratory of Molecular Genetics, Tsukuba Life Science Center, RIKEN, 3-1-1
      Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
FAU - Harada, J
AU  - Harada J
FAU - Tashiro, S
AU  - Tashiro S
FAU - Gotoh-Mandeville, R
AU  - Gotoh-Mandeville R
FAU - Maekawa, T
AU  - Maekawa T
FAU - Ishii, S
AU  - Ishii S
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ATF2 protein, human)
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Smad3 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
SB  - IM
MH  - Activating Transcription Factor 2
MH  - Animals
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Leucine Zippers
MH  - *MAP Kinase Kinase Kinases
MH  - Mammals
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction
MH  - Smad3 Protein
MH  - Trans-Activators/genetics/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Transforming Growth Factor beta/*metabolism
EDAT- 1999/03/20 00:00
MHDA- 1999/03/20 00:01
CRDT- 1999/03/20 00:00
PHST- 1999/03/20 00:00 [pubmed]
PHST- 1999/03/20 00:01 [medline]
PHST- 1999/03/20 00:00 [entrez]
AID - 10.1074/jbc.274.13.8949 [doi]
AID - S0021-9258(19)87417-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 26;274(13):8949-57. doi: 10.1074/jbc.274.13.8949.