New Modulators for IGF-I Activity within IGF-I Processing Products.
New Modulators for IGF-I Activity within IGF-I Processing Products.
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DOI：
10.3389/fendo.2013.00042
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发表时间：
2013
影响因子：
5.2
通讯作者：
Barton ER
中科院分区：
文献类型：
--
作者：
Brisson BK;Barton ER
胰岛素样生长因子I（IGF-I）是肌肉发育和生长的关键调节因子。由Igf 1基因产生的前原肽经过几个翻译后加工步骤，产生分泌的成熟蛋白，被认为是IGF-I受体（IGF-IR）的专性配体。然而，从Igf 1产生的其他形式和肽的意义尚不清楚。例如，C-末端延伸称为E-肽，其是pro-IGF-I的一部分，涉及在细胞生长中发挥作用，包括以IGF-IR独立的方式的细胞增殖和迁移以及肌肉肥大。然而，这些肽的活性一直存在争议。IGF-IR独立的行动表明存在的E-肽受体，但这样的蛋白质尚未被发现。我们提出一个新的概念：不存在E-肽受体，而是E-肽与IGF-I协调以调节IGF-IR的活性。越来越多的证据表明，E-肽的存在改变IGF-I活性，无论是作为前IGF-I的一部分，还是作为单独的肽。在这篇综述中，我们将检查过去的文献IGF-I加工和E-肽的行动在骨骼肌中，解决以前的尝试分离IGF-I和E-肽的影响，提出一个新的模型IGF-I/E-肽协同作用，并建议未来的实验来测试，如果E-肽真正调节IGF-I活性。
Insulin-like growth factor I (IGF-I) is a key regulator of muscle development and growth. The pre-pro-peptide produced by the Igf1 gene undergoes several post-translational processing steps to result in a secreted mature protein, which is thought to be the obligate ligand for the IGF-I receptor (IGF-IR). However, the significance of the additional forms and peptides produced from Igf1 is not clear. For instance, the C-terminal extensions called the E-peptides that are part of pro-IGF-I, have been implicated in playing roles in cell growth, including cell proliferation and migration and muscle hypertrophy in an IGF-IR independent manner. However, the activity of these peptides has been controversial. IGF-IR independent actions suggest the existence of an E-peptide receptor, yet such a protein has not been discovered. We propose a new concept: there is no E-peptide receptor, rather the E-peptides coordinate with IGF-I to modulate activity of the IGF-IR. Growing evidence reveals that the presence of an E-peptide alters IGF-I activity, whether as part of pro-IGF-I, or as a separate peptide. In this review, we will examine the past literature on IGF-I processing and E-peptide actions in skeletal muscle, address the previous attempts to separate IGF-I and E-peptide effects, propose a new model for IGF-I/E-peptide synergy, and suggest future experiments to test if the E-peptides truly modulate IGF-I activity.