RESUMO
Human Growth Hormone (hGH) includes two main variants. The first is 22kDa GH (22K-GH), which is predominant in the blood circulation. The second most abundant variant is 20K-GH, which makes up 5-10% of the blood circulation. Both bind and activate the same receptor, called the human growth hormone receptor (GHR). However, the reason why 22K-GH and 20K-GH exhibit similar, but not identical physiological activities remains poorly understood. In this article, the intracellular signalling profiles between these two hormones were examined. Western blot analyses were performed in 3T3-F442A and CHO cells transfected with GHR (CHO-GHR). The results revealed that both 22K-GH and 20K-GH can activate Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1, 3 and 5 (STATs 1/3/5). Both induced tyrosine phosphorylation of JAK2 and STAT/1/3/5 in a time-dependent and dose-dependent manner. However, there were significant differences in the intracellular signalling properties between 22K-GH and 20K-GH. In particular, the kinetics of signalling shown by 22K-GH and 20K-GH is different. In addition, we found that the 20K-GH-induced tyrosine phosphorylation of signalling proteins was weaker than that of 22K-GH. Together, these observations indicate that the levels and kinetics of phosphorylation mediated by the main signalling proteins triggered by 22K-GH or 20K-GH were not exactly the same. This may provide a possible explanation for the different biological activities exhibited by 22K-GH and 20K-GH.