| First Author | Jing X | Year | 2012 |
| Journal | Cell Rep | Volume | 2 |
| Issue | 3 | Pages | 652-65 |
| PubMed ID | 22999939 | Mgi Jnum | J:196226 |
| Mgi Id | MGI:5487490 | Doi | 10.1016/j.celrep.2012.08.021 |
| Citation | Jing X, et al. (2012) Crosstalk of humoral and cell-cell contact-mediated signals in postnatal body growth. Cell Rep 2(3):652-65 |
| abstractText | 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. |
