Ghrelin octanoylation mediated by an orphan lipid transferase

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-04, Vol.105 (17), p.6320-6325
Main Authors: Gutierrez, Jesus A, Solenberg, Patricia J, Perkins, Douglas R, Willency, Jill A, Knierman, Michael D, Jin, Zhaoyan, Witcher, Derrick R, Luo, Shuang, Onyia, Jude E, Hale, John E
Format: Article
Language:English
Subjects:
Acylation
Acyltransferases - genetics
Acyltransferases - metabolism
Animals
Biological Sciences
Caprylates - metabolism
Cell culture techniques
Cell Line, Tumor
Cell Membrane - enzymology
Complementary DNA
Conserved Sequence
Fatty acids
Gene Expression Profiling
Gene Expression Regulation, Enzymologic
Genetics
Ghrelin - blood
Ghrelin - genetics
Ghrelin - metabolism
Goats
Hormones
Humans
Insulin secretion
Lipids
Molecular Sequence Data
Pancreas
Pancreas - enzymology
Peptides
Peptides - metabolism
Proteins
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Serine - metabolism
Small interfering RNA
Stomach
Stomach - enzymology
Vertebrates
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0800708105