| 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
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565)
MC3T3-E1(RCB1126)
10T1/2(RCB0247)
C2C12(RCB0987) |
