Abstract
LONGTMR3IGF-I, an analogue of insulin-like growth factor (IGF)-I, was specifically engineered for use in biopharmaceutical protein production in mammalian cells. LONGTMR3IGF-I is capable of supporting the growth and survival of Chinese hamster ovary cells in serum-free media at concentrations at least 200-fold lower than required for insulin. LONGTMR3IGF-I also acts as a more potent growth and survival factor than either insulin or native IGF-I in SF culture of human embryonic kidney (HEK293) cells. To investigate the basis of the enhanced potency of LONGTMR3IGF-I we have examined the mechanism of action of these mitogens in HEK293 cells. All mitogens tested were found to activate the TypeI IGF receptor (IGF-IR) and insulin receptor (IR) in a dose-responsive manner. However, the level of activation of both receptors after stimulation with LONGTMR3IGF-I, at lower concentrations, was greater than with either insulin or IGF-I. The greater potency of LONGTMR3IGF-I in activating the IR, despite having a low affinity for IRs, suggests the presence of heterotetrameric IGF-IR/IR dimers. Interestingly, the decrease in IGF-IR activation at higher concentrations of LONGTMR3IGF-I suggests that the dose-response curve may be bell-shaped.
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Voorhamme, D., Yandell, C.A. LONGTMR3IGF-I as a more potent alternative to insulin in serum-free culture of HEK293 cells. Mol Biotechnol 34, 201–204 (2006). https://doi.org/10.1385/MB:34:2:201
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DOI: https://doi.org/10.1385/MB:34:2:201