Premium
Smad8/9 Is Regulated Through the BMP Pathway
Author(s) -
Katakawa Yuko,
Funaba Masayuki,
Murakami Masaru
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25478
Subject(s) - smad , microbiology and biotechnology , cycloheximide , signal transduction , bone morphogenetic protein 2 , phosphorylation , chemistry , biology , biochemistry , protein biosynthesis , in vitro
Members of the transforming growth factor‐β (TGF‐β) family function through Smad‐dependent and Smad‐independent pathways. The Smad‐dependent pathway is stimulated through the phosphorylation of receptor‐regulated Smad (R‐Smad) and inhibited through the dephosphorylation of R‐Smad or the gene induction of inhibitory Smad (I‐Smad). Little information is available on the regulation of R‐Smad gene expression. BMP4 potentiated the up‐regulation of Smad8/9 expression in C2C12, H9c2, 3T3‐L1, HepG2, B16, and primary fibroblasts. BMP4‐induced Smad8/9 expression was cycloheximide‐insensitive and LDN‐193189‐sensitive, suggesting a direct event mediated through BMP type I receptors. BMP4 transcriptionally stimulated the Smad8/9 gene, and BMP‐responsive elements (BREs) spanning nt −121 to nt −44 are involved in the up‐regulation of Smad8/9 expression in response to BMP4. Phosphorylated Smad1/5/8/9 specifically bound to the BREs of Smad8/9 gene. The present study reveals that Smad8/9 is a unique R‐Smad regulated through the BMP pathway at the mRNA level. J. Cell. Biochem. 117: 1788–1796, 2016. © 2016 Wiley Periodicals, Inc.