3．三量体Gタンパク質の脂質修飾

三量体Gタンパク質研究の現状

抄録

Guanine nucleotide-binding regulatory proteins (heterotrimeric G proteins) are composed of α-, β- and γ-subunits, and they mediate a variety of intracellular signal transductions by coupling activated membrane receptors with effector enzymes and channels. Activated receptors catalyze the exchange of GDP bound to the α-subunits for cytosolic GTP, and GTP-bound α-subunits in turn regulate activities or functions of the effectors. The βγ-complex is not dissociable under physiological conditions, and it is indispensable for the GDP/GTP exchange reaction on the α-subunit. Recently, three kinds of lipid modifications have been found in the α- and γ-subunits. The first is the attachment of fatty acids, myristate (C14:0) or structurally related fatty acids to the N-terminal glycine residues of some members of the α-subunits. Another type of fatty acylation to be characterized is the linkage of palmitate (C16:0) to a number of α-subunits via a thioester bond at their cysteine residues. The third type of modification is polyisoprenylation (farnesylation or geranylgeranylation) and α-carboxyl methylation at the C-terminal cysteine residue of the γ-subunit. These modifications on the two subunits have been shown to play a critical role in not only protein-membrane interaction but also proper protein-protein interaction, both of which are required for the G protein function.