Role of the TAK1-NLK-STAT3 pathway in TGF-β-mediated mesoderm induction
- Bisei Ohkawara1,5,
- Kyoko Shirakabe1,5,
- Junko Hyodo-Miura2,
- Ritsuko Matsuo1,
- Naoto Ueno2,
- Kunihiro Matsumoto3, and
- Hiroshi Shibuya1,4,6
- 1Department of Molecular Cell Biology, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, and CREST, JST, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan; 2Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan; 3Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, JST, Chikusa-ku, Nagoya 464-8602, Japan; 4Center of Excellence Program for Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan
Abstract
Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) and Nemo-like kinase (NLK) function in Xenopus, Drosophila, and Caenorhabditis elegans development. Here we report that serine phosphorylation of STAT3 induced by TAK1-NLK cascade is essential for TGF-β-mediated mesoderm induction in Xenopus embryo. Depletion of TAK1, NLK, or STAT3 blocks TGF-β-mediated mesoderm induction. Coexpression of NLK and STAT3 induces mesoderm by a mechanism that requires serine phosphorylation of STAT3. Activin activates NLK, which in turn directly phosphorylates STAT3. Moreover, depletion of either TAK1 or NLK inhibits endogenous serine phosphorylation of STAT3. These results provide the first evidence that TAK1-NLK-STAT3 cascade participates in TGF-β-mediated mesoderm induction.
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Footnotes
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1166904.
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↵5 These authors contributed equally to this work.
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↵6 Corresponding author.
↵6 E-MAIL shibuya.mcb{at}mri.tmd.ac.jp; FAX 81-3-5280-8062.
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- Accepted January 8, 2004.
- Received November 3, 2003.
- Cold Spring Harbor Laboratory Press
