Ghrelin octanoylation mediated by an orphan lipid transferase
Ghrelin octanoylation mediated by an orphan lipid transferase
复制标题
DOI：
10.1073/pnas.0800708105
复制
发表时间：
2008-04-29
影响因子：
11.1
通讯作者：
Hale, John E.
中科院分区：
文献类型：
--
作者：
Gutierrez, Jesus A.;Solenberg, Patricia J.;Hale, John E.
肽类激素胃饥饿素是已知唯一一种带有O -连接的辛酰基侧链修饰的蛋白质，该修饰发生在其第3个丝氨酸残基上。这种修饰对胃饥饿素的生理效应至关重要，包括对进食、肥胖和胰岛素分泌的调节。尽管辛酰化在胃饥饿素的生理过程中起着关键作用，但介导这种新型修饰的脂质转移酶一直不为人知。在此我们报道了人胃饥饿素O -酰基转移酶（GOAT）的鉴定和特性。GOAT是一种保守的孤儿膜结合O -酰基转移酶（MBOAT），它特异性地使胃饥饿素肽的丝氨酸 - 3发生辛酰化。GOAT和胃饥饿素的转录本主要出现在胃和胰腺中。GOAT在脊椎动物中是保守的，小鼠中GOAT基因的遗传破坏导致循环中完全没有酰化胃饥饿素。胃饥饿素和GOAT在胃和胰腺组织中的存在表明了GOAT在胃饥饿素酰化中的相关性，并进一步暗示了酰化胃饥饿素在胰腺功能中的作用。
The peptide hormone ghrelin is the only known protein modified with an O-linked octanoyl side group, which occurs on its third serine residue. This modification is crucial for ghrelin's physiological effects including regulation of feeding, adiposity, and insulin secretion. Despite the crucial role for octanoylation in the physiology of ghrelin, the lipid transferase that mediates this novel modification has remained unknown. Here we report the identification and characterization of human GOAT, the ghrelin O-acyl transferase. GOAT is a conserved orphan membrane-bound O-acyl transferase (MBOAT) that specifically octanoylates serine-3 of the ghrelin peptide. Transcripts for both GOAT and ghrelin occur predominantly in stomach and pancreas. GOAT is conserved across vertebrates, and genetic disruption of the GOAT gene in mice leads to complete absence of acylated ghrelin in circulation. The occurrence of ghrelin and GOAT in stomach and pancreas tissues demonstrates the relevance of GOAT in the acylation of ghrelin and further implicates acylated ghrelin in pancreatic function.