Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction

Transforming growth factor (TGF)-beta-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 fo TGF-beta-mediated mesoderm induction in...

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Bibliographic Details
Published in:Genes & development 2004-02, Vol.18 (4), p.381-386
Main Authors: Ohkawara, Bisei, Shirakabe, Kyoko, Hyodo-Miura, Junko, Matsuo, Ritsuko, Ueno, Naoto, Matsumoto, Kunihiro, Shibuya, Hiroshi
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
Caenorhabditis elegans
Caenorhabditis elegans - enzymology
Carrier Proteins - genetics
DNA-Binding Proteins - genetics
Drosophila
Drosophila - embryology
Embryo, Nonmammalian - physiology
Intracellular Signaling Peptides and Proteins
Mesoderm - physiology
Mitogen-Activated Protein Kinases - genetics
Mutagenesis, Site-Directed
NLK protein
Research Communications
STAT3 Transcription Factor
TAK1 protein
Trans-Activators - genetics
Transforming Growth Factor beta - physiology
Xenopus
Xenopus - embryology
Xenopus Proteins - genetics
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Summary:Transforming growth factor (TGF)-beta-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 fo TGF-beta-mediated mesoderm induction in Xenopus embryo. Depletion of TAK1, NLK, or STAT3 blocks TGF-beta-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-beta-mediated mesoderm induction.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1166904