Non-glycosylated IGF2 Prohormones Are More Mitogenic Than Native IGF2

Overview

Journal Commun Biol

Specialty Biology

Date 2023 Aug 19

PMID 37598269

Authors

Pavlo Potalitsyn

Lucie Mrazkova

Irena Selicharova

Michaela Tencerova

Michaela Ferencakova

Martina Chrudinova

Tereza Turnovska

Andrzej Marek Brzozowski

Ales Marek

Jakub Kaminsky

Jiri Jiracek

Lenka Zakova

Affiliations

Soon will be listed here.

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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