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Science 16 April 1999:
Vol. 284. no. 5413, pp. 479 - 482
DOI: 10.1126/science.284.5413.479
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Reports

Synergistic Signaling in Fetal Brain by STAT3-Smad1 Complex Bridged by p300

Kinichi Nakashima, 12 Makoto Yanagisawa, 1 Hirokazu Arakawa, 1 Naoki Kimura, 1 Tatsuhiro Hisatsune, 3 Masahiro Kawabata, 4 Kohei Miyazono, 4 Tetsuya Taga 1*

The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein-2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation-independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.

1 Department of Molecular Cell Biology,
2 Cell Fate Modulation Research Unit, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
3 Department of Applied Biological Chemistry, University of Tokyo, Tokyo 113-8857, Japan.
4 Department of Biochemistry, Cancer Institute, Japanese Foundation for Cancer Research, and Research for the Future Program, Japan Society for the Promotion of Science, Tokyo 170-8455, Japan.
*   To whom correspondence should be addressed. E-mail: tagamcb{at}mri.tmd.ac.jp

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Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.
W. Wang, F. V. Mariani, R. M. Harland, and K. Luo (2000)
PNAS 97, 14394-14399
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The transcriptional co-activator P/CAF potentiates TGF-{beta}/Smad signaling.
S. Itoh, J. Ericsson, J.-i. Nishikawa, C.-H. Heldin, and P. t. Dijke (2000)
Nucleic Acids Res. 28, 4291-4298
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TGF-{beta}1 and IFN-{gamma} Direct Macrophage Activation by TNF-{alpha} to Osteoclastic or Cytocidal Phenotype.
S. W. Fox, K. Fuller, K. E. Bayley, J. M. Lean, and T. J. Chambers (2000)
J. Immunol. 165, 4957-4963
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Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3.
C. Kawamura, M. Kizaki, K. Yamato, H. Uchida, Y. Fukuchi, Y. Hattori, T. Koseki, T. Nishihara, and Y. Ikeda (2000)
Blood 96, 2005-2011
   Abstract »    Full Text »    PDF »
Three Amino Acids Specify Coactivator Choice By Retinoid X Receptors.
G. Shao, R. A. Heyman, and I. G. Schulman (2000)
Mol. Endocrinol. 14, 1198-1209
   Abstract »    Full Text »
A novel Smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction.
R. H. Kim, D. Wang, M. Tsang, J. Martin, C. Huff, M. P. de Caestecker, W. T. Parks, X. Meng, R. J. Lechleider, T. Wang, et al. (2000)
Genes & Dev. 14, 1605-1616
   Abstract »    Full Text »
Leukemia-Inhibitory Factor--Neuroimmune Modulator of Endocrine Function.
C. J. Auernhammer and S. Melmed (2000)
Endocr. Rev. 21, 313-345
   Abstract »    Full Text »
Cooperation Among Stat1, Glucocorticoid Receptor, and PU.1 in Transcriptional Activation of the High-Affinity Fc{gamma} Receptor I in Monocytes.
S. Aittomaki, M. Pesu, B. Groner, O. A. Janne, J. J. Palvimo, and O. Silvennoinen (2000)
J. Immunol. 164, 5689-5697
   Abstract »    Full Text »    PDF »
TIEG proteins join the Smads as TGF-beta -regulated transcription factors that control pancreatic cell growth.
T. Cook and R. Urrutia (2000)
Am J Physiol Gastrointest Liver Physiol 278, G513-G521
   Abstract »    Full Text »    PDF »
Interleukin 6 Activates Androgen Receptor-mediated Gene Expression through a Signal Transducer and Activator of Transcription 3-dependent Pathway in LNCaP Prostate Cancer Cells.
T. Chen, L. H. Wang, and W. L. Farrar (2000)
Cancer Res. 60, 2132-2135
   Abstract »    Full Text »
Synergy of Activin and Ciliary Neurotrophic Factor Signaling Pathways in the Induction of Vasoactive Intestinal Peptide Gene Expression.
A. J. Symes, R. L. Pitts, J. Conover, K. Kos, and J. Coulombe (2000)
Mol. Endocrinol. 14, 429-439
   Abstract »    Full Text »
Characterization of a Bone Morphogenetic Protein-responsive Smad-binding Element.
K. Kusanagi, H. Inoue, Y. Ishidou, H. K. Mishima, M. Kawabata, and K. Miyazono (2000)
Mol. Biol. Cell 11, 555-565
   Abstract »    Full Text »
BMP-2/ALK3 and HGF signal in parallel to regulate renal collecting duct morphogenesis.
I. Gupta, M Macias-Silva, S Kim, X Zhou, T. Piscione, C Whiteside, J. Wrana, and N. Rosenblum (2000)
J. Cell Sci. 113, 269-278
   Abstract »    PDF »
Interdependent SMAD and JNK Signaling in Transforming Growth Factor-beta -mediated Transcription.
M. E. Engel, M. A. McDonnell, B. K. Law, and H. L. Moses (1999)
J. Biol. Chem. 274, 37413-37420
   Abstract »    Full Text »    PDF »


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