Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2

Potalitsyn, P.; Mrazkova, L.; Selicharova, I.; Tencerova, M.; Ferencakova, M.; Chrudinova, M.; Brzozowski, A. M.; Marek, A.; Kaminsky, J.; Jiracek, J.; Zakova, L.

doi:10.1101/2023.01.16.524179

bioRxiv · 10.1101/2023.01.16.524179

Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2

Potalitsyn, P.·Mrazkova, L.·Selicharova, I.·Tencerova, M.·Ferencakova, M.·Chrudinova, M.·Brzozowski, A. M.·Marek, A.·Kaminsky, J.·Jiracek, J.·Zakova, L.

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Abstract

Insulin-like Growth Factor-2 (IGF2) is important for the regulation of human embryonic growth and development, and for adults physiology. Incorrect processing of the IGF2 precursor, pro-IGF2(156), leads to the formation of two IGF2 proforms, big-IGF2(87) and big-IGF2(104). Unprocessed and mainly non-glycosylated IGF2 proforms are found at abnormally high levels in certain diseases, but their mode of action is still unclear. Here, we found that pro-IGF2(156) has the lowest ability to form its inactivating complexes with IGF-Binding Proteins and has higher proliferative properties in cells than IGF2 and other IGF prohormones. We also showed that big-IGF2(104) has a seven-fold higher binding affinity for the IGF2 receptor than IGF2, and that pro-IGF2(87) binds and activates specific receptors and stimulates cell growth similarly to the mature IGF2. The properties of these pro-IGF2 forms, especially of pro-IGF2(156) and big-IGF2(104), indicate them as hormones that may be associated with human diseases related to the accumulation of IGF-2 proforms in the circulation.

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Potalitsyn, P., Mrazkova, L., Selicharova, I., Tencerova, M., Ferencakova, M., Chrudinova, M., Brzozowski, A. M., Marek, A., Kaminsky, J., Jiracek, J., Zakova, L.. 2023-01-18. Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2. https://doi.org/10.1101/2023.01.16.524179

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