Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280).
Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280).
复制标题
多巴胺 D(3) 受体与肌动蛋白结合蛋白 280 (ABP-280) 的关联。
DOI：
10.1016/s0006-2952(01)00932-7
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发表时间：
2002
影响因子：
5.8
通讯作者：
Zhou,QunYong
中科院分区：
文献类型：
--
作者：
Li,Ming;Li,Chuanyu;Weingarten,Paul;Bunzow,JamesR;Grandy,DavidK;Zhou,QunYong
与G蛋白偶联受体结合的蛋白质已被鉴定为受体定位和信号传导的调节剂。在我们以前的研究中，发现一种细胞骨架蛋白，肌动蛋白结合蛋白280（ABP-280），与多巴胺D2受体的第三个胞质环相关。在本研究中，我们证明ABP-280也与多巴胺D3受体相互作用，但不与D4受体相互作用。与多巴胺D2受体类似，D3/ABP-280的结合具有信号传导的重要性。在缺乏ABP-280的人黑色素瘤M2细胞中，D3受体不能显著抑制毛喉素刺激的cAMP（cAMP）产生。然而，在ABP-280缺陷型M2细胞和ABP-280重组型M2亚克隆（A7细胞）中，D4受体对毛喉素刺激的cAMP产生的抑制程度相似。进一步的实验表明，D3/ABP-280相互作用主要依赖于D3受体第三环的36个氨基酸的羧基结构域，该结构域在D2受体中是保守的，但在D4受体中不是。我们的研究结果表明细胞骨架蛋白ABP-280对多巴胺D2家族受体信号传导具有亚型特异性调节作用。
Proteins that bind to G protein-coupled receptors have been identified as regulators of receptor localization and signaling. In our previous studies, a cytoskeletal protein, actin-binding protein 280 (ABP-280), was found to associate with the third cytoplasmic loop of dopamine D2receptors. In this study, we demonstrate that ABP-280 also interacts with dopamine D3receptors, but not with D4receptors. Similar to the dopamine D2receptor, the D3/ABP-280 association is of signaling importance. In human melanoma M2 cells lacking ABP-280, D3receptors were unable to inhibit forskolin-stimulated cyclic AMP (cAMP) production significantly. D4receptors, however, exhibited a similar degree of inhibition of forskolin-stimulated cAMP production in ABP-280-deficient M2 cells and ABP-280-replent M2 subclones (A7 cells). Further experiments revealed that the D3/ABP-280 interaction was critically dependent upon a 36 amino acid carboxyl domain of the D3receptor third loop, which is conserved in the D2receptor but not in the D4receptor. Our results demonstrate a subtype-specific regulation of dopamine D2-family receptor signaling by the cytoskeletal protein ABP-280.