Potalitsyn, Pavlo, Mrázková, Lucie, Selicharová, Irena et al. (9 more authors) (2023) Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2. Communications Biology. 863. ISSN 2399-3642
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Funding Information: This work was supported by the Czech Science Foundation grant No. 19-14069S (to L.Z.), by the European Regional Development Fund, OP RDE, Project: “Chemical Biology for drugging undruggable targets (ChemBioDrug)” (No. CZ.02.1.01/0.0/0.0/16_019/0000729), by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID Project No. LX22NPO5104, Funded by the European Union-Next Generation EU), and by the Academy of Sciences of the Czech Republic (Research Project RVO:6138963, support to the Institute of Organic Chemistry and Biochemistry). A.M.B. was supported by MRC grant MR/R009066/1 and BBSRC grant BB/W003783/1. © The Author(s) 2023 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 06 Sep 2023 11:30 |
Last Modified: | 16 Oct 2024 19:25 |
Published Version: | https://doi.org/10.1038/s42003-023-05239-6 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s42003-023-05239-6 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:203116 |
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Description: Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2
Licence: CC-BY 2.5