Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2.
Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2.
复制标题
DOI：
10.1038/s42003-023-05239-6
复制
发表时间：
2023-08-19
影响因子：
5.9
通讯作者：
Zakova, Lenka
中科院分区：
文献类型：
--
作者：
Potalitsyn, Pavlo;Mrazkova, Lucie;Selicharova, Irena;Tencerova, Michaela;Ferencakova, Michaela;Chrudinova, Martina;Turnovska, Tereza;Brzozowski, Andrzej Marek;Marek, Ales;Kaminsky, Jakub;Jiracek, Jiri;Zakova, Lenka
胰岛素样生长因子-2(IGF2)对调节人类胚胎生长发育和成人生理具有重要意义。对IGF2前体PRO-IGF2(156)的错误处理导致形成两种IGF2构型，BIG-IGF2(87)和BIG-IGF2(104)。在某些疾病中，未加工且主要是非糖基化的IGF2形式被发现异常高水平，但它们的作用模式仍不清楚。在这里，我们发现原IGF2(156)与IGF结合蛋白形成失活复合体的能力最低，在细胞中具有比IGF2和其他IGF前激素更高的增殖特性。我们还发现BIG-IGF2(104)与IGF2受体的结合亲和力是IGF2的7倍，并且PRO-IGF2(87)与特定的受体结合并激活，并刺激细胞生长，类似于成熟的IGF2。这些前-IGF2形式的性质，特别是前-IGF2(156)和BIG-IGF2(104)，表明它们可能是与人类疾病有关的激素，与循环中IGF-2形式的积累有关。比较三种胰岛素样生长因子-2非糖基化产物的结合和激活能力，发现ProIGF2(156)和BIG-IGF2(104)可能是与疾病相关的蓄积激素。
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. 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.
登录
查看更多内容
影响因子：
4
作者：
Chu, Chun-Hsien;Tzang, Bor-Show;Huang, Chih-Yang
通讯作者：
Huang, Chih-Yang
影响因子：
5.8
作者：
BAXTER，RC;HOLMAN，Susan R.;BRAUND，W
通讯作者：
BRAUND，W
影响因子：
4.8
作者：
Duguay, SJ;Jin, Y;Steiner, DF
通讯作者：
Steiner, DF
影响因子：
1.4
作者：
Fukuda, Izumi;Hizuka, Naomi;Takano, Kazue
通讯作者：
Takano, Kazue
影响因子：
4
作者：
Bond, JJ;Meka, S;Baxter, RC
通讯作者：
Baxter, RC