Year: 2023
Type: article
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.
Source: Communications Biology
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
Awards: G12500569, G1647388553, G176604203, G1767254865, G277992333, G291036901, G3382653560, G3490171961, G3622461675, The structure-activity study of peptides derived from pro-IGF2 playing a role in the pathogenesis of cancer, type 2 diabetes and osteoporosis., G4131035492, MICA: A molecular dissection of the interplay between diabetes and cancer: an integrated, multidisciplinary approach. II., Revealing Molecular Bases of Signal Transduction through the Drosophila Insulin Receptor: cryoEM and Functional Studies., G5664899889, G5916014575, G7363506711, G7542731269, G8292427812, G845074391, G8790023787
OpenAlex ID: W4386001747