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 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.
Ohkawara
Bisei
B
Department 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.
Shirakabe
Kyoko
K
Hyodo-Miura
Junko
J
Matsuo
Ritsuko
R
Ueno
Naoto
N
Matsumoto
Kunihiro
K
Shibuya
Hiroshi
H
D019943:Amino Acid Substitution; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology; D002352:Carrier Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D010749:Phosphoprotein Phosphatases; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050796:STAT3 Transcription Factor; C099510:TAB1 protein, MAPKKK activator, vertebrate; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D020928:Mitogen-Activated Protein Kinases; C462720:nemo like kinase, Xenopus; D010749:Phosphoprotein Phosphatases; C486301:TAB1 protein, Xenopus