Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2
Comparison of binding and activation abilities for all three Insulin-like Growth Factor-2 unglycosylated proforms shows that proforms proIGF2(156) and big-IGF2(104) may be disease-associated accumulating hormones.
Insulin-like Growth Factor-2 (IGF2) plays a crucial role in regulating human embryonic growth and development, as well as adult 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). Research has found that unprocessed and mainly non-glycosylated IGF2 proforms are elevated at abnormal levels in certain diseases. However, the mode of action of these proforms remains unclear. In this study, researchers compared the binding and activation abilities of the three Insulin-like Growth Factor-2 unglycosylated proforms. They found that pro-IGF2(156) had the lowest ability to form its inactivating complexes with IGF-Binding Proteins. Instead, pro-IGF2(156) exhibited higher proliferative properties in cells than IGF2 and other IGF prohormones. Furthermore, big-IGF2(104) had a seven-fold higher binding affinity for the IGF2 receptor than IGF2, indicating it may be a hormone associated with human diseases. Big-IGF2(104) also bound and activated specific receptors, stimulating cell growth similarly to mature IGF2. The properties of these pro-IGF2 forms, particularly pro-IGF2(156) and big-IGF2(104), suggest they may be disease-associated hormones. The findings of this study highlight the importance of understanding the role of IGF2 proforms in human disease. However, it is essential to note that these results do not imply a causal relationship between the proforms and disease. Further research is necessary to fully elucidate the mechanisms underlying the actions of IGF2 proforms. Moreover, the study's results should not be used to diagnose or treat diseases related to IGF2 proforms without medical supervision.