RECEPTOR REGULATION OF G-PROTEIN PALMITOYLATION
RECEPTOR REGULATION OF G-PROTEIN PALMITOYLATION
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DOI：
10.1073/pnas.91.7.2800
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发表时间：
1994-03-29
影响因子：
11.1
通讯作者：
GILMAN, AG
中科院分区：
文献类型：
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作者：
MUMBY, SM;KLEUSS, C;GILMAN, AG
许多异三聚体鸟嘌呤核苷酸结合调节蛋白（G蛋白）的α亚基被棕榈酰化。细胞暴露于β -肾上腺素能激动剂异丙肾上腺素会增加[H-3]棕榈酸酯特异性地与α (s)结合，α亚基介导腺苷酸环化酶的刺激。脉冲追踪实验表明异丙肾上腺素增加了α (s)结合棕榈酸酯的周转。在α (s)或α (o)（一个同源α亚基）中的Cys-3突变阻止了这些蛋白的棕榈酰化。当细胞中表达α (s)或α (o)中的Cys-3突变并测定其在可溶性和膜组分之间的分布时，得到了不同的结果。一些α亚基，包括α (o)，在氨基末端甘氨酸残基上发生肉豆蔻酰化。这种甘氨酸的突变阻止了α (o)的肉豆蔻酰化和棕榈酰化，表明肉豆蔻酰化先于双酰化α亚基的棕榈酰化。双酰化α亚基的氨基末端序列和脂肪酰化特性与Src蛋白酪氨酸激酶家族的一些成员惊人地相似。这些蛋白共享的氨基末端序列Met-Gly-Cvs-Xaa-Xaa-Ser/Cys可能代表了共翻译和翻译后加工的基序，包括甘氨酸残基的肉豆醇酰化和半胱氨酸残基的可逆棕榈酰化。
Many alpha subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) are palmitoylated. Exposure of cells to the beta-adrenergic agonist isoproterenol increased incorporation of [H-3]palmitate specifically into alpha(s), the alpha subunit that mediates stimulation of adenylyl cyclase. Pulse-chase experiments suggested that isoproterenol increased turnover of alpha(s)-bound palmitate. Mutagenesis of Cys-3 in alpha(s) or alpha(o) (a homologous alpha subunit) prevented palmitoylation of these proteins. Differing results were obtained when mutations of Cys-3 in alpha(s) or alpha(o) were expressed in cells and assayed for their distribution between soluble and membrane fractions. Some alpha subunits, including alpha(o), are myristoylated at the amino-terminal glycine residue. Mutation of this glycine prevented both myristoylation and palmitoylation of alpha(o), indicating that myristoylation precedes palmitoylation of dually acylated alpha subunits. The amino-terminal sequences and fatty acylation properties of dually acylated alpha subunits are strikingly similar to those of some members of the Src family of protein-tyrosine kinases. The amino-terminal sequence Met-Gly-Cvs-Xaa-Xaa-Ser/Cys shared by these proteins may represent a motif for cotranslational and posttranslational processing that includes myristoylation of the glycine residue and reversible palmitoylation of the cysteine residue.