Duncan J A, Gilman A G
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
J Biol Chem. 1998 Jun 19;273(25):15830-7. doi: 10.1074/jbc.273.25.15830.
Thioacylation is one of a handful of reversible covalent protein modifications, but the enzymes responsible for addition and removal of long chain fatty acids from protein cysteine residues in vivo have not yet been identified. The alpha subunits of some heterotrimeric G proteins cycle between thioacylated and deacylated states in a receptor-regulated fashion. We have identified, purified, and characterized an enzyme acyl-protein thioesterase that deacylates Galpha proteins and at least some other thioacyl protein substrates, including Ha-RAS. The action of this enzyme on thioacylated heterotrimeric Gs is regulated by activation of the G protein. Although native and recombinant acyl-protein thioesterases act as both acyl-protein thioesterases and lysophospholipases in vitro, we demonstrate by transfection that the enzyme can accelerate the turnover of thioacyl groups on Gsalpha in vivo.
硫酰化是少数几种可逆的共价蛋白质修饰之一，但负责在体内从蛋白质半胱氨酸残基添加和去除长链脂肪酸的酶尚未被鉴定出来。一些异源三聚体G蛋白的α亚基以受体调节的方式在硫酰化和去酰化状态之间循环。我们已经鉴定、纯化并表征了一种酶——酰基蛋白硫酯酶，它能使Gα蛋白以及至少一些其他硫酰化蛋白底物（包括Ha-RAS）去酰化。该酶对硫酰化异源三聚体Gs的作用受G蛋白激活的调节。尽管天然和重组的酰基蛋白硫酯酶在体外既作为酰基蛋白硫酯酶又作为溶血磷脂酶起作用，但我们通过转染证明该酶在体内可以加速Gsα上硫酰基的周转。
