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The Activation and Differential Signalling of the Growth Hormone Receptor Induced by pGH or Anti-Idiotypic Monoclonal Antibodies in Primary Rat Hepatocytes

The Activation and Differential Signalling of the Growth Hormone Receptor Induced by pGH or Anti-Idiotypic Monoclonal Antibodies in Primary Rat Hepatocytes

Wei Li, Hainan Lan, Huimin Liu, Zhiling Fu, Yanhong Yang, Weiwei Han, Feng Guo, Yu Liu, Hui Zhang, Jingsheng Liu, Xin Zheng

Mol Cell Endocrinol. 2013 Aug 25;376(1-2):51-9.

PMID: 23769824

Abstract:

In this report, we have developed a panel of monoclonal anti-idiotypic antibodies to pGH by immunising BALB/c mice with a purified monoclonal anti-pGH antibody (1A3), among which one mAb, termed CG-8F, was selected for further characterisation. We found that CG-8F behaved as a typical Ab2β, not only conformationally competing with pGH for 1A3 but also exhibiting recognition for GHR in a rat hepatocyte model. We next examined the resulting signal transduction pathways triggered by this antibody in rat hepatocytes and found that both pGH and CG-8F could trigger the JAK2-STAT1/3/5-mediated signal transduction pathway. Furthermore, the phosphorylation kinetics of pSTAT1/3/5 induced by either pGH or CG-8F were remarkably similar in the dose-response and time course rat hepatocyte experiments. In contrast, only pGH, but not CG-8F, was capable of inducing ERK phosphorylation. Further experimental studies indicated that the two functional binding sites on CG-8F are required for GHR activation. This study partially reveals the mechanism of action of GH anti-idiotypic antibodies and also indicates that monoclonal anti-idiotypic antibodies represent an effective way to produce GH mimics, suggesting that it is possible to produce signal-specific cytokine agonists using an anti-idiotypic antibody approach.

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