沃尔特·坎农是一位备受尊敬的美国神经学家和生理学家，具有非常广泛的兴趣。以坎农及其广泛兴趣为传统，我们讨论了我们实验室在信号转导方面多方面的工作，涵盖了过去40多年。我们展示了我们对血液中生长激素（GH）如何与身体各部分的细胞进行通信以促进身体生长和调节身体新陈代谢的问题的质疑，从而不仅对身高有了认识，还对恶性肿瘤和体重的重要调节因子有了了解。亮点包括：1）GH信号传导的关键初始步骤是GH激活GH受体相关的酪氨酸激酶JAK2；2）GH激活JAK2导致一系列信号传导蛋白的激活，包括STAT转录因子；3）JAK2在多个酪氨酸上自磷酸化，调节JAK2的活性并招募信号传导蛋白到GH/GH受体/JAK2复合物中；4）活化的STAT蛋白与癌症相关；5）GH激活JAK2招募适配蛋白SH2B1到GH/GH受体/JAK2复合物中，在其中促进GH对肌动蛋白细胞骨架和运动性的调节；6）SH2B1被招募到大脑中的其他受体中，在其中增强饱腹感，很可能部分通过调节瘦素作用和调节食欲调节神经元的连接来实现。这些发现增加了我们对GH功能的理解，也为某些癌症和肥胖个体的治疗干预提供了依据，从而加强了支持基础研究的重要性，因为人们事先无法预知它可以提供什么重要的见解。

Walter Cannon was a highly regarded American neurologist and physiologist with extremely broad interests. In the tradition of Cannon and his broad interests, we discuss our laboratory's multi-faceted work in signal transduction over the past 40+ years. We show how our questioning of how growth hormone (GH) in the blood communicates with cells throughout the body to promote body growth and regulate body metabolism led to insight into not only body height, but also important regulators of malignancy and body weight. Highlights include finding that: 1) A critical initiating step in GH signal transduction is GH activating the GH receptor-associated tyrosine kinase JAK2; 2) GH activation of JAK2 leads to activation of a number of signaling proteins, including STAT transcription factors; 3) JAK2 is autophosphorylated on multiple tyrosines that regulate the activity of JAK2 and recruit signaling proteins to GH/GH receptor/JAK2 complexes; 4) Constitutively activated STAT proteins are associated with cancer; 5) GH activation of JAK2 recruits the adapter protein SH2B1 to GH/GH receptor/JAK2 complexes where it facilitates GH regulation of the actin cytoskeleton and motility; 6) SH2B1 is recruited to other receptors in the brain, where it enhances satiety, most likely in part by regulating leptin action and neuronal connections of appetite-regulating neurons. These findings have led to increased understanding of how GH functions, as well as therapeutic interventions for certain cancer and obese individuals, thereby reinforcing the great importance of supporting basic research, since one never knows ahead of time what important insight it can provide.