Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth
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 re...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002616 |
| _version_ | 1828772732459810816 |
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| author | Xuefeng Jing Masayasu Miyajima Takahiro Sawada Qingfa Chen Keiji Iida Kenryo Furushima Daiki Arai Kazuo Chihara Kazushige Sakaguchi |
| author_facet | Xuefeng Jing Masayasu Miyajima Takahiro Sawada Qingfa Chen Keiji Iida Kenryo Furushima Daiki Arai Kazuo Chihara Kazushige Sakaguchi |
| author_sort | Xuefeng Jing |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T14:50:06Z |
| format | Article |
| id | doaj.art-76f310b2993b4e38a75442cd91e28ff3 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T14:50:06Z |
| publishDate | 2012-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-76f310b2993b4e38a75442cd91e28ff32022-12-22T01:01:30ZengElsevierCell Reports2211-12472012-09-012365266510.1016/j.celrep.2012.08.021Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body GrowthXuefeng Jing0Masayasu Miyajima1Takahiro Sawada2Qingfa Chen3Keiji Iida4Kenryo Furushima5Daiki Arai6Kazuo Chihara7Kazushige Sakaguchi8Department of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanLaboratory Animal Center, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanDepartment of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanDepartment of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanDepartment of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanDepartment of Molecular Cell Biology and Molecular Medicine, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, JapanThe 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.http://www.sciencedirect.com/science/article/pii/S2211124712002616 |
| spellingShingle | Xuefeng Jing Masayasu Miyajima Takahiro Sawada Qingfa Chen Keiji Iida Kenryo Furushima Daiki Arai Kazuo Chihara Kazushige Sakaguchi Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth Cell Reports |
| title | Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth |
| title_full | Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth |
| title_fullStr | Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth |
| title_full_unstemmed | Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth |
| title_short | Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth |
| title_sort | crosstalk of humoral and cell cell contact mediated signals in postnatal body growth |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712002616 |
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