β-arrestin-dependent formation of β2 adrenergic receptor Src protein kinase complexes
β-arrestin-dependent formation of β2 adrenergic receptor Src protein kinase complexes
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DOI：
10.1126/science.283.5402.655
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发表时间：
1999-01-29
期刊：
影响因子：
56.9
通讯作者：
Lefkowitz, RJ
中科院分区：
文献类型：
--
作者：
Luttrell, LM;Ferguson, SSG;Lefkowitz, RJ
许多与异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）偶联的受体对促分裂原活化蛋白（MAP）激酶途径的PAS依赖性激活需要Src家族酪氨酸激酶的激活。刺激β 2肾上腺素能受体导致含有活化的c-Src和受体的蛋白质复合物的组装。Src的募集是由β-抑制蛋白介导的，β-抑制蛋白作为衔接蛋白，结合c-Src和激动剂占据的受体。β-Arrestin 1突变体在c-Src结合或将受体靶向网格蛋白包被的小窝的能力方面受损，作为β 2肾上腺素能受体介导的MAP激酶Erk 1和Erk 2活化的显性负性抑制剂。这些数据表明，β-抑制蛋白结合，终止受体-C蛋白偶联，也启动了第二波信号转导，其中“脱敏”受体作为促有丝分裂信号传导复合物的关键结构组分发挥作用。
The Pas-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of beta(2) adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by beta-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. beta-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of beta(2) adrenergic receptor-mediated activation of the MAP kinases Erk1 and Erk2. These data suggest that beta-arrestin binding, which terminates receptor-C protein;coupling, also initiates a second wave of signal transduction in which the "desensitized" receptor functions as a critical structural component of a mitogenic signaling complex.