Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone

Jing Yang; Michael S. Brown; Guosheng Liang; Nick V. Grishin; Joseph L. Goldstein

doi:10.1016/j.cell.2008.01.017

Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone

Jing Yang, Michael S. Brown, Guosheng Liang, Nick V. Grishin, Joseph L. Goldstein

Research output: Contribution to journal › Article › peer-review

980 Scopus citations

Abstract

Ghrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans.

Original language	English (US)
Pages (from-to)	387-396
Number of pages	10
Journal	Cell
Volume	132
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2008.01.017
State	Published - Feb 8 2008

Keywords

CHEMBIO
HUMDISEASE
PROTEINS

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2008.01.017

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title = "Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone",

abstract = "Ghrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans.",

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author = "Jing Yang and Brown, {Michael S.} and Guosheng Liang and Grishin, {Nick V.} and Goldstein, {Joseph L.}",

note = "Funding Information: We thank the following colleagues for helpful suggestions: Hyock Kwon (ghrelin electrophoresis and reverse-phase chromatography); Lisa N. Kinch (bioinformatics); and Soo Hee Lee (fatty acid methyl ester analysis). We also thank Lisa Beatty and Angela Carroll for invaluable assistance with tissue culture; Richard Gibson and Y.K. Ho for help with antibodies; and Monica Mendoza for help with animals. This work was supported by grants from National Institutes of Health (HL20948) and Perot Family Foundation. G.L. is a recipient of an Individual Biomedical Research Award from the Hartwell Foundation. ",

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AU - Grishin, Nick V.

AU - Goldstein, Joseph L.

N1 - Funding Information: We thank the following colleagues for helpful suggestions: Hyock Kwon (ghrelin electrophoresis and reverse-phase chromatography); Lisa N. Kinch (bioinformatics); and Soo Hee Lee (fatty acid methyl ester analysis). We also thank Lisa Beatty and Angela Carroll for invaluable assistance with tissue culture; Richard Gibson and Y.K. Ho for help with antibodies; and Monica Mendoza for help with animals. This work was supported by grants from National Institutes of Health (HL20948) and Perot Family Foundation. G.L. is a recipient of an Individual Biomedical Research Award from the Hartwell Foundation.

PY - 2008/2/8

Y1 - 2008/2/8

N2 - Ghrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans.

AB - Ghrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans.

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Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone

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