Genetic and molecular analysis of growth retardation caused by growth hormone insensitivity

GH被认为是出生后机体生长的必需激素，主要通过肝脏等组织中IGF1的产生起作用，整个信号过程被命名为GH-IGF1轴。我们发现EphA4是GHR的重要结合伙伴。EphA4结合GHR并增强JAK2/STAT5B通路的激活。此外，EphA4直接结合并磷酸化STAT5B。通过这些相互作用，EphA4转录增强肝细胞和其他细胞中IGF1的产生。Epha4 KO小鼠以Epha4基因剂量依赖的方式显示身材矮小，并且对IGF1反应良好，但对GH治疗没有反应。

GH is regarded as an essential hormone for postnatal body growth that mainly works through IGF1 production in liver and other tissues, and the whole signaling process is named GH-IGF1 axis. We identified EphA4 as an essential binding partner of GHR. EphA4 binds to GHR and augments activation of the JAK2/STAT5B pathway. In addition, EphA4 directly binds to and phosphorylates STAT5B. Through these interactions, EphA4 transcriptionally enhances IGF1 production in liver cells as well as in others. Epha4 KO mice show short stature in an Epha4 gene dose-dependent fashion, and respond well to IGF1 but not to GH treatment.