Smad mediates BMP-2-induced upregulation of FGF-evoked PC12 cell differentiation.
We previously reported that bone morphogenetic protein (BMP)-2 augments fibroblast growth factor (FGF)-induced neuronal differentiation of PC12 cells by selectively upregulating FGF receptor (FGFR)-1 expression. Here we describe the underlying mechanism. BMP-2 activated Smad proteins in PC12 cells. Overexpression of Smad7 or Smad1, inhibitory and receptor-regulated isoforms, respectively, suppressed or enhanced BMP-2-induced upregulation of FGFR-1 expression. Smad 7 also inhibited the FGF-induced PC12 differentiation. Our findings indicate that activation of a Smad signaling pathway is required for upregulation of FGFR-1 expression by BMP-2 and for the synergistic induction of PC12 differentiation by BMP-2 and FGF.
Hayashi
Hisaki
H
Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan.
Ishisaki
Akira
A
Imamura
Toru
T
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D004357:Drug Synergism; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000502:physiology*; D016212:Transforming Growth Factor beta; D015854:Up-Regulation
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D051785:Smad Proteins; D051898:Smad1 Protein; C497400:Smad1 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1