Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction.
How do very diverse signaling pathways induce neural differentiation in Xenopus? Anti-BMP (Chordin), FGF8, and IGF2 signals are integrated in the embryo via the regulation of Smad1 phosphorylation. Neural induction results from the combined inhibition of BMP receptor serine/threonine kinases and activation of receptor tyrosine kinases that signal through MAPK and phosphorylate Smad1 in the linker region, further inhibiting Smad1 transcriptional activity. This hard-wired molecular mechanism at the level of the Smad1 transcription factor may help explain the opposing activities of IGF, FGF, and BMP signals not only in neural induction, but also in other aspects of vertebrate development.
Pera
Edgar M
EM
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California-Los Angeles, Los Angeles, CA 90095-1662, USA.
Ikeda
Atsushi
A
Eivers
Edward
E
De Robertis
Eddy M
EM
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000494:pharmacology; D009420:Nervous System / Q000196:embryology*; D010766:Phosphorylation; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D029867:Xenopus Proteins; D014982:Xenopus laevis
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; C497402:MXD1 protein, Xenopus; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D015534:Trans-Activators; D029867:Xenopus Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D007335:Insulin-Like Growth Factor II; D020928:Mitogen-Activated Protein Kinases; D052004:Bone Morphogenetic Protein Receptors