hide
Free keywords:
Amino Acid Sequence
Animals
Catalytic Domain
Cell Line, Tumor
Escherichia coli/genetics
GTP-Binding Protein alpha Subunits, Gi-Go/genetics/*metabolism
GTP-Binding Protein alpha Subunits, Gq-G11/genetics/*metabolism
GTP-Binding Proteins/genetics/*metabolism
Gene Expression
Glutamine/genetics/metabolism
Histamine/genetics/*metabolism
Mass Spectrometry
Mastocytoma/enzymology/genetics
Mice
Molecular Sequence Data
*Protein Processing, Post-Translational
Proteome/genetics/metabolism
Recombinant Fusion Proteins/genetics/metabolism
Signal Transduction/genetics
Transglutaminases/genetics/*metabolism
cdc42 GTP-Binding Protein/genetics/*metabolism
Abstract:
Posttranslational modifications (PTM) have been shown to be essential for protein function and signaling. Here we report the identification of a novel modification, protein transfer of histamine, and provide evidence for its function in G protein signaling. Histamine, known as neurotransmitter and mediator of the inflammatory response, was found incorporated into mastocytoma proteins. Histaminylation was dependent on transglutaminase II. Mass spectrometry confirmed histamine modification of the small and heterotrimeric G proteins Cdc42, Galphao1 and Galphaq. The modification was specific for glutamine residues in the catalytic core, and triggered their constitutive activation. TGM2-mediated histaminylation is thus a novel PTM that functions in G protein signaling. Protein alphamonoaminylations, thus including histaminylation, serotonylation, dopaminylation and norepinephrinylation, hence emerge as a novel class of regulatory PTMs.
