On the processing of proghrelin to ghrelin
On the processing of proghrelin to ghrelin
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DOI：
10.1074/jbc.m607955200
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发表时间：
2006-12-15
影响因子：
4.8
通讯作者：
Steiner, Donald F.
中科院分区：
文献类型：
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作者：
Zhu, Xiaorong;Cao, Yun;Steiner, Donald F.
促食欲激素ghrelin是一种由99个氨基酸的前体衍生的28个氨基酸的肽，并在Ser-3处酰化，其最初从大鼠胃中分离。除了刺激食欲和生长外，它还在能量平衡以及心血管和免疫系统中发挥各种重要作用。虽然其生理作用的分析已经取得了许多有意义的结果，但关于其生物合成及其酰化机制的信息却少得多。在这份报告中，我们已经研究了这个分子从其前体（促生长素释放肽）到成熟的促生长素释放肽在各种激素原转化酶无效的小鼠品系在我们的实验室中产生的内蛋白水解加工，并确定了转化酶负责这一事件。使用蛋白质印迹法、质谱法和免疫细胞化学方法，我们已经证明：（a）在小鼠胃中，激素原转化酶1/3（PC 1/3）是负责将促生长素释放肽转化为促生长素释放肽的内切蛋白酶;（B）该肽的酰化是不依赖于加工的;（c）在加工缺陷（PC 1/3缺失）小鼠中促生长素释放肽mRNA的表达增加。
The orexigenic hormone ghrelin is a 28-amino-acid peptide derived from a 99-amino-acid precursor and acylated at Ser-3, which was initially isolated from rat stomach. In addition to stimulating appetite and growth, it also plays various important roles in energy homeostasis and in the cardiovascular and immune systems. Although analysis of its physiological effects has yielded many significant results, much less information is available on its biosynthesis and the mechanism of its acylation. In this report, we have studied the endoproteolytic processing of this molecule from its precursor (proghrelin) into mature ghrelin in various prohormone convertase null mouse strains generated in our laboratory and have identified the convertase responsible for this event. Using Western blotting, mass spectrometry, and immunocytochemical methods, we have demonstrated that (a) in mouse stomach, prohormone convertase 1/3 (PC1/3) is the endoprotease responsible for the conversion of proghrelin to ghrelin, (b) the acylation of this peptide is processing-independent, and (c) the expression of proghrelin mRNA is increased in the processing-deficient (PC1/3 null) mouse.