Molecular effects of proinsulin C-peptide
Molecular effects of proinsulin C-peptide
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DOI：
10.1016/s0006-291x(02)00721-0
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发表时间：
2002-08-02
影响因子：
3.1
通讯作者：
Jörnvall, H
中科院分区：
文献类型：
--
作者：
Johansson, J;Ekberg, K;Jörnvall, H
胰岛素原c肽一直被认为只是胰岛素生物合成的副产物，但最近的报道表明，它引起了分子和生理作用，表明它是一种激素活性肽。c肽与完整细胞的质膜和清洁剂溶解细胞的特异性结合已被证明，表明存在c肽的细胞表面受体。c肽引起许多细胞反应，包括Ca2+内流、有丝分裂原活化蛋白（MAP）激酶、Na+、K+- atp酶和内皮NO合成酶的激活。与人c肽c端5个残基对应的五肽EGSLQ，模拟了全长肽的几种作用。该五肽取代细胞膜结合的c肽，引起细胞内Ca2+浓度的短暂增加，并刺激MAP激酶信号通路和Na+，K+- atp酶。五肽的Glu残基对于全长c肽的位移是必不可少的，游离的Glu可以部分位移结合的c肽，这表明电荷相互作用对受体结合很重要。许多c肽的作用，如map -激酶erk1和2的磷酸化，Na+，K+- atp酶的刺激和细胞内钙浓度的增加被百日咳毒素抑制，支持c肽与g蛋白偶联受体的相互作用。然而，并不是所有的c肽效应都能用这种方式来解释，可能还涉及到其他的相互作用。综上所述，现有的观察结果表明c肽具有生物活性，并提出了其生理作用的分子模型。(C) 2002 Elsevier Science （USA）。版权所有。
The proinsulin C-peptide has been held to be merely a by-product in insulin biosynthesis, but recent reports show that it elicits both molecular and physiological effects, suggesting that it is a hormonally active peptide. Specific binding of C-peptide to the plasma membranes of intact cells and to detergent-solubilised cells has been shown, indicating the existence of a cell surface receptor for C-peptide. C-peptide elicits a number of cellular responses, including Ca2+ influx, activation of mitogen-activated protein (MAP) kinases, of Na+,K+-ATPase, and of endothelial NO synthase. The pentapeptide EGSLQ, corresponding to the C-terminal five residues of human C-peptide, mimics several of the effects of the full-length peptide. The pentapeptide displaces cell membrane-bound C-peptide, elicits transient increase in intracellular Ca2+ concentration and stimulates MAP kinase signalling pathways and Na+,K+-ATPase. The Glu residue of the pentapeptide is essential for displacement of the full-length C-peptide, and free Glu can partly displace bound C-peptide, suggesting that charge interactions are important for receptor binding. Many C-peptide effects, such as phosphorylation of MAP-kinases ERK 1 and 2, stimulation of Na+,K+-ATPase and increases in intracellular calcium concentrations are inhibited by pertussis toxin, supporting interaction of C-peptide with a G-protein-coupled receptor. However, all C-peptide effects cannot be explained in this manner, and it is possible that additional interactions are involved. Combined, the available observations show that C-peptide is biologically active and suggest a molecular model for its physiological effects. (C) 2002 Elsevier Science (USA). All rights reserved.