Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.
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.
Nakashima
K
K
Department of Molecular Cell Biology, Cell Fate Modulation Research Unit, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Yanagisawa
M
M
Arakawa
H
H
Kimura
N
N
Hisatsune
T
T
Kawabata
M
M
Miyazono
K
K
Taga
T
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D019556:COS Cells; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050881:E1A-Associated p300 Protein; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D017978:Receptors, Growth Factor; D053606:Receptors, OSM-LIF; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D017978:Receptors, Growth Factor; D053606:Receptors, OSM-LIF; D050796:STAT3 Transcription Factor; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D052004:Bone Morphogenetic Protein Receptors