McDonald P H, Lefkowitz R J
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.
Cell Signal. 2001 Oct;13(10):683-9. doi: 10.1016/s0898-6568(01)00203-0.
The last few years have seen a marked expansion in appreciation of the diversity of roles played by the betaArrestins in regulating GPCR functions. Originally discovered as molecules that desensitize such receptors, the roles of betaArrestins have expanded to include acting as signalling adapters or intermediates that recruit other key molecules to the GPCRs in an agonist-regulated fashion. For example, interactions with components of the endocytic machinery, such as clathrin, the adapter protein AP-2 and the N-ethylmaleimide sensitive fusion protein (NSF), demonstrate the ability of betaArrestins to act as adapters to facilitate the clathrin-mediated endocytosis of certain members of the GPCR family. BetaArrestins have also been shown to serve as signalling molecules. The Ras-dependent activation of ERK1/2 may involve the betaArrestin-dependent recruitment of c-Src to the beta2-adrenergic receptor (beta2-AR). More recently, betaArrestins have been shown to act as molecular scaffolds that coordinate the assembly of certain MAP kinase complexes that lead to the stimulation of either ERK1/2 or JNK3. Finally, long-term accumulation of arrestin-rhodopsin complexes, in photoreceptor cells has been shown to trigger apoptosis.
在过去几年中，人们对β抑制蛋白在调节G蛋白偶联受体（GPCR）功能中所起的多种作用的认识有了显著扩展。β抑制蛋白最初被发现是使此类受体脱敏的分子，其作用现已扩展到包括作为信号转导衔接子或中间体，以激动剂调节的方式将其他关键分子招募到GPCRs。例如，与内吞机制成分的相互作用，如网格蛋白、衔接蛋白AP - 2和N - 乙基马来酰亚胺敏感融合蛋白（NSF），证明了β抑制蛋白作为衔接子促进GPCR家族某些成员网格蛋白介导的内吞作用的能力。β抑制蛋白也已被证明可作为信号分子。ERK1/2的Ras依赖性激活可能涉及β抑制蛋白依赖性地将c - Src招募到β2 - 肾上腺素能受体（β2 - AR）。最近，β抑制蛋白已被证明可作为分子支架，协调某些导致ERK1/2或JNK3激活的丝裂原活化蛋白激酶（MAP）复合物的组装。最后，已证明在光感受器细胞中抑制蛋白 - 视紫红质复合物的长期积累会触发细胞凋亡。
