Heptahelical terpsichory. Who calls the tune?
Heptahelical terpsichory. Who calls the tune?
复制标题
DOI：
10.1080/10799890801941921
复制
发表时间：
2008-01-01
影响因子：
2.8
通讯作者：
Luttrell, Louis M.
中科院分区：
文献类型：
--
作者：
Gesty-Palmer, Diane;Luttrell, Louis M.
视紫红质抑制蛋白可以作为配体调节的信号转导支架，这一发现揭示了 G 蛋白偶联受体 (GPCR) 信号转导中以前未被认识到的复杂性。由于抑制蛋白结合的 GPCR 与 G 蛋白解偶联，因此抑制蛋白结合可被视为在两种时间和空间上不同的信号传导模式之间切换受体。最近的工作确定了两个因素，强调了 GPCR 信号的这种双重性，并表明它最终可能具有治疗意义。第一个是受体抑制蛋白“信号组”的信号传导不需要异源三聚体 G 蛋白激活。第二个是抑制蛋白依赖性信号可以由通路特异性“偏向激动剂”启动，从而创造了选择性调节 GPCR 功能不同方面的药物的潜力。然而，目前，人们对细胞或整个动物水平上 G 蛋白独立信号的生理相关性知之甚少，并且需要进行额外的工作来确定抑制蛋白途径选择性药物是否会找到临床应用。
The discovery that arrestins can function as ligand-regulated signaling scaffolds has revealed a previously unappreciated level of complexity in G protein-coupled receptor (GPCR) signal transduction. Because arrestin-bound GPCRs are uncoupled from G proteins, arrestin binding can be viewed as switching receptors between two temporally and spatially distinct signaling modes. Recent work has established two factors that underscore this duality of GPCR signaling and suggest it may ultimately have therapeutic significance. The first is that signaling by receptor-arrestin "signalsomes" does not require heterotrimeric G protein activation. The second is that arrestin-dependent signals can be initiated by pathway-specific "biased agonists," creating the potential for drugs that selectively modulate different aspects of GPCR function. Currently, however, little is known about the physiological relevance of G protein-independent signals at the cellular or whole animal levels, and additional work is needed to determine whether arrestin pathway-selective drugs will find clinical application.