Miller W E, Lefkowitz R J
Howard Hughes Medical Institute, Department of Medicine, Box 3821, Duke University Medical Center, Durham, North Carolina 27710, USA.
Curr Opin Cell Biol. 2001 Apr;13(2):139-45. doi: 10.1016/s0955-0674(00)00190-3.
beta-arrestins play previously unsuspected and important roles as adapters and scaffolds that localize signaling proteins to ligand-activated G-protein-coupled receptors. As with the paradigmatic role of the beta-arrestins in uncoupling receptors from G proteins (desensitization), these novel functions involve the interaction of beta-arrestin with phosphorylated heptahelical receptors. beta-arrestins interact with at least two main classes of signaling proteins. First, interaction with molecules such as clathrin, AP-2 and NSF directs the clathrin-mediated internalization of G-protein-coupled receptors. Second, interaction with molecules such as Src, Raf, Erk, ASK1 and JNK3 appears to regulate several pathways that result in the activation of MAP kinases. These recent discoveries indicate that the beta-arrestins play widespread roles as scaffolds and/or adapter molecules that organize a variety of complex signaling pathways emanating from heptahelical receptors. It is likely that additional roles for the beta-arrestins remain to be discovered.
β抑制蛋白作为衔接蛋白和支架蛋白，将信号蛋白定位到配体激活的G蛋白偶联受体上，发挥着此前未被怀疑的重要作用。与β抑制蛋白在使受体与G蛋白解偶联（脱敏）中的典型作用一样，这些新功能涉及β抑制蛋白与磷酸化七螺旋受体的相互作用。β抑制蛋白与至少两类主要的信号蛋白相互作用。首先，与网格蛋白、AP - 2和NSF等分子的相互作用引导网格蛋白介导的G蛋白偶联受体的内化。其次，与Src、Raf、Erk、ASK1和JNK3等分子的相互作用似乎调节了导致MAP激酶激活的几种途径。这些最新发现表明，β抑制蛋白作为支架和/或衔接分子发挥着广泛作用，组织了源自七螺旋受体的各种复杂信号通路。β抑制蛋白可能还有其他作用有待发现。
