[PDF][PDF] Crosstalk of humoral and cell-cell contact-mediated signals in postnatal body growth

X Jing, M Miyajima, T Sawada, Q Chen, K Iida… - Cell Reports, 2012 - cell.com
X Jing, M Miyajima, T Sawada, Q Chen, K Iida, K Furushima, D Arai, K Chihara, K Sakaguchi
Cell Reports, 2012cell.com
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 …
Summary
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.
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