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Stearic acid blunts growth-factor signaling via oleoylation of GNAI proteins

Abstract - Covalent attachment of C16:0 to proteins (palmitoylation) regulates protein function. Proteins are also S-acylated by other fatty acids including C18:0. Whether protein acylation with different fatty acids has different functional outcomes is not well studied. We show here tha...

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Main Authors: Nůsková, Hana (Author) , Serebryakova, Marina V. (Author) , Ferrer-Caelles, Anna (Author) , Sachsenheimer, Timo (Author) , Lüchtenborg, Christian (Author) , Miller, Aubry K. (Author) , Brügger, Britta (Author) , Kordyukova, Larisa V. (Author) , Teleman, Aurelio A. (Author)
Format: Article (Journal)
Language:English
Published: 28 July 2021
In: Nature Communications
Year: 2021, Volume: 12, Pages: 1-15
ISSN:2041-1723
DOI:10.1038/s41467-021-24844-9
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-021-24844-9
Verlag, lizenzpflichtig, Volltext: http://www.nature.com/articles/s41467-021-24844-9
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Author Notes:Hana Nůsková, Marina V. Serebryakova, Anna Ferrer-Caelles, Timo Sachsenheimer, Christian Lüchtenborg, Aubry K. Miller, Britta Brügger, Larisa V. Kordyukova & Aurelio A. Teleman
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Summary:Abstract - Covalent attachment of C16:0 to proteins (palmitoylation) regulates protein function. Proteins are also S-acylated by other fatty acids including C18:0. Whether protein acylation with different fatty acids has different functional outcomes is not well studied. We show here that C18:0 (stearate) and C18:1 (oleate) compete with C16:0 to S-acylate Cys3 of GNAI proteins. C18:0 becomes desaturated so that C18:0 and C18:1 both cause S-oleoylation of GNAI. Exposure of cells to C16:0 or C18:0 shifts GNAI acylation towards palmitoylation or oleoylation, respectively. Oleoylation causes GNAI proteins to shift out of cell membrane detergent-resistant fractions where they potentiate EGFR signaling. Consequently, exposure of cells to C18:0 reduces recruitment of Gab1 to EGFR and reduces AKT activation. This provides a molecular mechanism for the anti-tumor effects of C18:0, uncovers a mechanistic link how metabolites affect cell signaling, and provides evidence that the identity of the fatty acid acylating a protein can have functional consequences.
Item Description:Gesehen am 26.09.2021
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-021-24844-9

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