Induction of Smad6 mRNA by bone morphogenetic proteins.
Members of the transforming growth factor-beta (TGF-beta) superfamily transduce signals via Smad proteins. Smad2 and Smad3 mediate TGF-beta signaling, whereas Smad1 and Smad5 transduce bone morphogenetic protein (BMP) signals. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 are recently identified members in the Smad family; they inhibit the signaling activity of the other Smad proteins. Here we show that expression of the Smad6 mRNA is dramatically induced by BMP-2 or osteogenic protein-1 (OP-1)/BMP-7 in various cells. BMP-2 induced expression of Smad7 in one cell type, although much less potently than that of Smad6. Smad6 message was induced by TGF-beta 1 in TGF-beta 1-responsive Mv1Lu cells, but the induction was transient in contrast to the induction by BMPs. These results indicate that Smad6 may form a feedback loop to regulate the signaling activity of BMPs.
Takase
M
M
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Imamura
T
T
Sampath
T K
TK
Takeda
K
K
Ichijo
H
H
Miyazono
K
K
Kawabata
M
M
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008168:Lung; D051379:Mice; D008809:Mice, Inbred C3H; D008907:Mink; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D051905:Smad6 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; D012333:RNA, Messenger; C497802:SMAD6 protein, human; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta