論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 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) |