Regulation of MAP kinase by the BMP-4/TAK1 pathway in Xenopus ectoderm.
Bone morphogenetic protein-4 (BMP-4) induces epidermis and represses neural fate in Xenopus ectoderm. Our previous findings implicate p42 Erk MAP kinase (MAPK) in the response to neural induction. We have examined the effects of BMP-4 on MAPK activity in gastrula ectoderm. Expression of a dominant negative BMP-4 receptor resulted in a 4.5-fold elevation in MAPK activity in midgastrula ectoderm. MAPK activity was reduced in ectoderm expressing a constitutively active BMP-4 receptor, or ectoderm treated with BMP-4 protein in the presence or absence of cycloheximide. Overexpression of TAK1 led to a reduction in MAPK activity in early gastrula ectoderm. The inhibitory effects of TAK1 could be reversed by 1 microM SB 203580, a p38 inhibitor. Treatment of isolated ectoderm with SB 203580 led to expression of otx2, NCAM, and noggin. Western blot analyses indicated that the BMP-4 pathway does not activate JNKs in ectoderm. Our findings indicate that BMP-4 inhibits ectodermal MAPK activity through a TAK1/p38-type pathway. MAPK has been shown to inactivate Smad1. Thus, our results suggest that BMP-4 and MAPK pathways are mutually antagonistic in Xenopus ectoderm, and that interactions between these pathways may govern the choice between epidermal and neural fate.
Goswami
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Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5513, USA.
Uzgare
A R
AR
Sater
A K
AK
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004475:Ectoderm / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005775:Gastrula / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051857:Otx Transcription Factors; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases; D000099176:Noggin Protein; D000099151:MAP Kinase Kinase Kinase 7
D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D007093:Imidazoles; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D051857:Otx Transcription Factors; D011506:Proteins; D011725:Pyridines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D000099176:Noggin Protein; D000099151:MAP Kinase Kinase Kinase 7; C497661:Otx2 protein, Xenopus; C525812:bmp4 protein, Xenopus; C093642:SB 203580