RRC ID 37766
著者 Murakami M, Kawachi H, Ogawa K, Nishino Y, Funaba M.
タイトル Receptor expression modulates the specificity of transforming growth factor-beta signaling pathways.
ジャーナル Genes Cells
Abstract In current models of transforming growth factor-beta (TGF-beta) family signaling, type II receptors activate specific activin receptor-like kinase (ALK) type I receptors. These serine/threonine kinases activate ligand-dependent receptor regulated (R)-Smad by phosphorylating carboxy-terminal serines. We found that the receptor expression levels affected the phosphorylation and activation of the two R-Smad subclasses, activin/TGF-beta-specific (AR-Smad) and bone morphogenetic protein (BMP)-specific (BR-Smad). Co-expressing constitutively active type I and type II receptors in COS7 cells resulted in the phosphorylation of both R-Smad subclasses in a ligand-independent manner. This was verified using in vitro kinase assays. In untransfected B16 melanoma cells, TGF-beta1 and BMP-2 induced phosphorylation of both R-Smad subclasses, and TGF-beta1 up-regulated the inhibitor of differentiation (Id) gene, which is usually regulated by BMP. By contrast, BMP-2 up-regulated plasminogen activator inhibitor-1 (PAI-1), which is an AR-Smad-regulated gene. Except for ALK4 and ALK6, levels of type I and type II receptor mRNAs were higher in B16 cells than in HeLa and HepG2 cells, in which TGF-beta1 and BMP-2 induced phosphorylation of only the expected R-Smad. These results help to explain the diverse effects of this ligand family.
巻・号 14(4)
ページ 469-82
公開日 2009-4-1
DOI 10.1111/j.1365-2443.2009.01283.x
PII GTC1283
PMID 19335617
MeSH Activin Receptors, Type I / genetics Activin Receptors, Type I / metabolism* Animals Blotting, Western Bone Morphogenetic Protein 2 / pharmacology COS Cells Cell Line Cell Line, Tumor Chlorocebus aethiops Dose-Response Relationship, Drug Gene Expression HeLa Cells Humans Imidazoles / pharmacology Immunoprecipitation Mice Phosphorylation / drug effects Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Pyridines / pharmacology RNA Interference Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta / genetics Receptors, Transforming Growth Factor beta / metabolism* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* Smad Proteins, Receptor-Regulated / genetics Smad Proteins, Receptor-Regulated / metabolism* Transforming Growth Factor beta1 / pharmacology
IF 1.655
引用数 41
WOS 分野 GENETICS & HEREDITY CELL BIOLOGY
リソース情報
ヒト・動物細胞 COS-7(RCB0539) HeLa(RCB0007) Hep G2 MC3T3-E1(RCB1126) RAW 264(RCB0535)