Differential Nucleocytoplasmic Shuttling of β-Arrestins

Autor: Stefano Marullo, Erwann Le Rouzic, Mark G.H. Scott, Axel Périanin, Vincenzo Pierotti, Alexandre Benmerah, Serge Benichou, Hervé Enslen
Rok vydání: 2002
Předmět:
Zdroj: Journal of Biological Chemistry. 277:37693-37701
ISSN: 0021-9258
DOI: 10.1074/jbc.m207552200
Popis: β-arrestins (βarrs) are two highly homologous proteins that uncouple G protein-coupled receptors from their cognate G proteins, serve as adaptor molecules linking G protein-coupled receptors to clathrin-coat components (AP-2 complex and clathrin), and act as scaffolding proteins for ERK1/2 and JNK3 cascades. A striking difference between the two βarrs (βarr1 and βarr2) is that βarr1 is evenly distributed throughout the cell, whereas βarr2 shows an apparent cytoplasmic localization at steady state. Here, we investigate the molecular determinants underlying this differential distribution. βarr2 is constitutively excluded from the nucleus by a leptomycin B-sensitive pathway because of the presence of a classical leucine-rich nuclear export signal in its C terminus (L395/L397) that is absent in βarr1. In addition, using a nuclear import assay in yeast we showed that βarr2 is actively imported into the nucleus, suggesting that βarr2 undergoes constitutive nucleocytoplasmic shuttling. In cells expressing βarr2, JNK3 is mostly cytosolic. A point mutation of the nuclear export signal (L395A) in βarr2, which was sufficient to redistribute βarr2 from the cytosol to the nucleus, also caused the nuclear relocalization of JNK3. These data indicate that the nucleocytoplasmic shuttling of βarr2 controls the subcellular distribution of JNK3.
Databáze: OpenAIRE