Cross-linking transglutaminases with G protein-coupled receptor signaling.
Transglutaminases are a family of calcium- and thiol-dependent acyl transferases that catalyze the formation of an amide bond between the gamma-carboxamide groups of peptide-bound glutamine residues and the primary amino groups in various compounds, including the epsilon-amino group of lysines in certain proteins. As a result, these enzymes effect posttranslational modification of proteins by amine incorporation, or stabilization of protein assemblies by their cross-linking; such actions profoundly influence critical biological processes such as blood clotting and protection from infection and dehydration by establishing the barrier function of skin. In addition, transglutaminases have other more diverse actions, including involvement in signaling by the superfamily of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) in one of three ways: (i) through actions as guanosine triphosphate-binding proteins that activate intracellular effectors, such as phospholipase C; (ii) by cross-linking GPCR monomers to enhance signaling as a result of covalent dimer formation; or (iii) by interacting with an apparent growth inhibitory orphan GPCR, GPR56, to limit metastatic spread of melanoma cells. The implications of these receptor-coupled actions of transglutaminases are discussed.
Iismaa
Siiri E
SE
Molecular Cardiology Program, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.
Begg
Gillian E
GE
Graham
Robert M
RM
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D011503:Transglutaminases / Q000378:metabolism*
C118925:ADGRG1 protein, human; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins