| RRC ID |
44063
|
| 著者 |
Jing X, Miyajima M, Sawada T, Chen Q, Iida K, Furushima K, Arai D, Chihara K, Sakaguchi K.
|
| タイトル |
Crosstalk of humoral and cell-cell contact-mediated signals in postnatal body growth.
|
| ジャーナル |
Cell Rep
|
| Abstract |
The growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis mediates postnatal body growth. The GH receptor has been regarded as the sole receptor that mediates the Janus kinase 2 (JAK2)/signal transducers and activators of the transcription 5B (STAT5B) signal toward IGF1 synthesis. Here, we report a signaling pathway that regulates postnatal body growth through EphA4, a member of the Eph family of receptor tyrosine kinases and a mediator of the cell-cell contact-mediated signaling. EphA4 forms a complex with the GH receptor, JAK2, and STAT5B and enhances Igf1 expression predominantly via the JAK2-dependent pathway, with some direct effect on STAT5B. Mice with a defective Epha4 gene have a gene dose-dependent short stature and low plasma IGF1 levels. Igf1 messenger RNA (mRNA) in the liver and many other tissues was also significantly reduced in Epha4-knockout mice, whereas pituitary Gh mRNA and plasma GH levels were not. These findings suggest that the local cell-cell contact-mediated ephrin/EphA4 signal is as important as the humoral GH signal in IGF1 synthesis and body size determination.
|
| 巻・号 |
2(3)
|
| ページ |
652-65
|
| 公開日 |
2012-9-27
|
| DOI |
10.1016/j.celrep.2012.08.021
|
| PII |
S2211-1247(12)00261-6
|
| PMID |
22999939
|
| MeSH |
Animals
Body Size / physiology*
Cell Communication / physiology*
Gene Dosage
Growth Hormone / genetics
Growth Hormone / metabolism*
Humans
Insulin-Like Growth Factor I / genetics
Insulin-Like Growth Factor I / metabolism*
Janus Kinase 2 / genetics
Janus Kinase 2 / metabolism
Mice
Mice, Mutant Strains
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor, EphA4 / genetics
Receptor, EphA4 / metabolism
Receptors, Somatotropin / genetics
Receptors, Somatotropin / metabolism*
STAT5 Transcription Factor / genetics
STAT5 Transcription Factor / metabolism
Signal Transduction / physiology*
|
| IF |
8.109
|
| 引用数 |
12
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2 |
