Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2

0574400 - ÚOCHB 2024 RIV GB eng J - Journal Article
Potalitsyn, Pavlo - Mrázková, Lucie - Selicharová, Irena - Tencerová, Michaela - Ferenčáková, Michaela - Chrudinová, Martina - Turnovská, Tereza - Brzozowski, A. M. - Marek, Aleš - Kaminský, Jakub - Jiráček, Jiří - Žáková, Lenka
Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2.
Communications Biology. Roč. 6, č. 1 (2023), č. článku 863. E-ISSN 2399-3642
R&D Projects: GA ČR(CZ) GA19-14069S; GA MŠMT(CZ) EF16_019/0000729; GA MŠMT(CZ) LX22NPO5104
Institutional support: RVO:61388963 ; RVO:67985823
Keywords : hormone * prohormone * precursor * mitogenic * receptor * IGF
OECD category: Biochemistry and molecular biology
Impact factor: 5.9, year: 2022
Method of publishing: Open access
https://doi.org/10.1038/s42003-023-05239-6

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.
Permanent Link: https://hdl.handle.net/11104/0344735