Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor.
Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor.
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发表时间：
1989-05
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通讯作者：
B. O'dowd;M. Hnatowich;M. Caron;R. Lefkowitz;M. Bouvier
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作者：
B. O'dowd;M. Hnatowich;M. Caron;R. Lefkowitz;M. Bouvier
我们报道了人类β 2-肾上腺素能受体（β 2AR）中的半胱氨酸残基通过与棕榈酸的硫酯化共价修饰。通过受体的定点诱变，我们已经确定了该蛋白羧基尾部的Cys341是最可能的棕榈酰化位点。Cys341对甘氨酸的突变导致受体的非棕榈酰化形式，表现出介导异丙肾上腺素刺激腺苷酸环化酶的能力急剧降低。这种突变的β 2AR的功能损伤也反映在对激动剂形成鸟苷核苷酸敏感的高亲和力状态的能力显著降低，这是野生型受体的特征。这些结果表明，棕榈酸酯对β 2AR的翻译后修饰可能在受体与腺苷酸环化酶信号转导系统的正常偶联中起着至关重要的作用。
We report that a cysteine residue in the human beta 2-adrenergic receptor (beta 2AR) is covalently modified by thioesterification with palmitic acid. By site-directed mutagenesis of the receptor, we have identified Cys341 in the carboxyl tail of the protein as the most likely site of palmitoylation. Mutation of Cys341 to glycine results in a nonpalmitoylated form of the receptor that exhibits a drastically reduced ability to mediate isoproterenol stimulation of adenylyl cyclase. The functional impairment of this mutated beta 2AR is also reflected in a markedly reduced ability to form a guanyl nucleotide-sensitive high affinity state for agonists, characteristic of wild-type receptor. These results indicate that post-translational modification by palmitate of beta 2AR may play a crucial role in the normal coupling of the receptor to the adenylyl cyclase signal transduction system.