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

GH被认为是一种出生后身体生长所必需的激素，主要通过肝脏等组织中IGF1的产生来发挥作用，整个信号传递过程被称为GH-IGF1轴。我们确定EphA4是GHR的重要结合伙伴。EphA4与GHR结合，增强JAK2/STAT5B通路的激活。此外，EphA4直接与STAT5B结合并磷酸化。通过这些相互作用，EphA4在转录上促进了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表现出矮小的身材，对IGF1反应良好，但对GH处理不起作用。

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.