論文 - 詳細
| RRC ID | 61865 |
|---|---|
| 著者 | Fujita T, Meguro T, Fukuyama R, Nakamuta H, Koida M. |
| タイトル | New signaling pathway for parathyroid hormone and cyclic AMP action on extracellular-regulated kinase and cell proliferation in bone cells. Checkpoint of modulation by cyclic AMP. |
| ジャーナル | J Biol Chem |
| Abstract |
cAMP signaling, activated by extracellular stimuli such as parathyroid hormone, has cell type-specific effects important for cellular proliferation and differentiation in bone cells. Recent evidence of a second enzyme target for cAMP suggests divergent effects on extracellular-regulated kinase (ERK) activity depending on Epac/Rap1/B-Raf signaling. We investigated the molecular mechanism of the dual functionality of cAMP on cell proliferation in clonal bone cell types. MC3T3-E1 and ATDC5, but not MG63, express a 95-kDa isoform of B-Raf. cAMP stimulated Ras-independent and Rap1-dependent ERK phosphorylation and cell proliferation in B-Raf-expressing cells, but inhibited growth in B-Raf-lacking cells. The mitogenic action of cAMP was blocked by the ERK pathway inhibitor PD98059. In B-Raf-transduced MG63 cells, cAMP stimulated ERK activation and cell proliferation. Thus, B-Raf is the dominant molecular switch that permits differential cAMP-dependent regulation of ERK with important implications for cell proliferation in bone cells. These findings might explain the dual functionality of parathyroid hormone on osteoblastic cell proliferation. |
| 巻・号 | 277(25) |
| ページ | 22191-200 |
| 公開日 | 2002-6-21 |
| DOI | 10.1074/jbc.M110364200 |
| PII | S0021-9258(19)66802-X |
| PMID | 11956184 |
| MeSH | 3T3 Cells Animals Blotting, Northern Bone and Bones / cytology* Cell Division Cell Line Cyclic AMP / metabolism* Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Genes, Dominant Humans Immunoblotting Mice Mice, Inbred C3H Mitogen-Activated Protein Kinases / metabolism* PC12 Cells Parathyroid Hormone / metabolism* Phosphorylation Protein Isoforms RNA, Messenger / metabolism Rats Signal Transduction* Skull / metabolism Time Factors Tissue Distribution Tumor Cells, Cultured rap1 GTP-Binding Proteins / metabolism |
| IF | 4.238 |
| 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 | ATDC5(RCB0565) MC3T3-E1(RCB1126) 10T1/2(RCB0247) C2C12(RCB0987) |