| RRC ID |
41494
|
| 著者 |
Suzawa M, Tamura Y, Fukumoto S, Miyazono K, Fujita T, Kato S, Takeuchi Y.
|
| タイトル |
Stimulation of Smad1 transcriptional activity by Ras-extracellular signal-regulated kinase pathway: a possible mechanism for collagen-dependent osteoblastic differentiation.
|
| ジャーナル |
J Bone Miner Res
|
| Abstract |
Signals from bone morphogenetic protein receptors (BMPRs) and cell adhesion to type I collagen are both important for osteoblastic differentiation and functions. BMP signals are mediated mostly by Smad and collagen signals are transduced by integrins to activate focal adhesion kinase (FAK) and its downstream molecules. This study was undertaken to clarify how extracellular matrix collagen signals converge with BMP actions. We show that integrin activation by collagen was involved in BMP signals because disruption of either collagen synthesis or collagen-alpha2beta1-integrin binding inhibited the stimulatory effect of BMP-2 on osteoblastic MC3T3-E1 cells. Downstream signals of collagen-integrin might be FAK-Ras-extracellular signal-regulated kinase (ERK) in osteoblastic cells. We further show that Ras-ERK signals enhanced the transcriptional activity of Smad1 in response to BMP in these cells transiently transfected with expression plasmids for a constitutively active mutant RasV12, a dominant negative mutant RasN17, and an ERK phosphatase CL100. Ras-ERK signals did not augment the transcriptional activity of Smad3 in response to transforming growth factor beta (TGF-beta) receptor activation but that of Smad1 in response to BMPR activation as examined in COS-1 cells. These observations suggest that the Ras-ERK pathway downstream of integrin-FAK is involved in Smad1 signals activated by BMP and provide a possible mechanism for cooperation between intracellular signals activated by integrin and BMPRs in osteoblastic cells.
|
| 巻・号 |
17(2)
|
| ページ |
240-8
|
| 公開日 |
2002-2-1
|
| DOI |
10.1359/jbmr.2002.17.2.240
|
| PMID |
11811554
|
| MeSH |
Activin Receptors, Type I / genetics
Activin Receptors, Type I / metabolism
Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / metabolism*
Bone Morphogenetic Proteins / pharmacology
Cell Differentiation
Cells, Cultured
Collagen / metabolism*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Enzyme Inhibitors / pharmacology
Epidermal Growth Factor / pharmacology
Flavonoids / pharmacology
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
Integrins / metabolism
Mice
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / drug effects
Mitogen-Activated Protein Kinases / metabolism*
Osteoblasts / cytology
Osteoblasts / drug effects
Osteoblasts / metabolism*
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / metabolism
Receptor, Transforming Growth Factor-beta Type I
Receptors, Collagen
Receptors, Transforming Growth Factor beta / genetics
Receptors, Transforming Growth Factor beta / metabolism
Signal Transduction
Smad Proteins
Smad1 Protein
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcription, Genetic
Transforming Growth Factor beta*
ras Proteins / metabolism*
|
| IF |
5.854
|
| 引用数 |
74
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
HOS(RCB0992) |
