Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sites.

Song X, Gurevich EV, Gurevich VV
J Neurochem. 2007 103 (3): 1053-62

PMID: 17680991 · PMCID: PMC2430867 · DOI:10.1111/j.1471-4159.2007.04842.x

Arrestins are multi-functional regulators of G protein-coupled receptors. Receptor-bound arrestins interact with >30 remarkably diverse proteins and redirect the signaling to G protein-independent pathways. The functions of free arrestins are poorly understood, and the interaction sites of the non-receptor arrestin partners are largely unknown. In this study, we show that cone arrestin, the least studied member of the family, binds c-Jun N-terminal kinase (JNK3) and Mdm2 and regulates their subcellular distribution. Using arrestin mutants with increased or reduced structural flexibility, we demonstrate that arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin 'frozen' in the basal state. To localize the interaction sites, we expressed separate N- and C-domains of cone and rod arrestins and found that individual domains bind JNK3 and remove it from the nucleus as efficiently as full-length proteins. Thus, the arrestin binding site for JNK3 includes elements in both domains with the affinity of partial sites on individual domains sufficient for JNK3 relocalization. N-domain of rod arrestin binds Mdm2, which localizes its main interaction site to this region. Comparable binding of JNK3 and Mdm2 to four arrestin subtypes allowed us to identify conserved residues likely involved in these interactions.

MeSH Terms (21)

Active Transport, Cell Nucleus Ambystoma Animals Arrestin Binding Sites Cell Compartmentation Cell Line Cell Nucleus Cytoplasm Green Fluorescent Proteins Humans Indoles Mitogen-Activated Protein Kinase 10 Protein Binding Protein Conformation Protein Structure, Tertiary Protein Transport Proto-Oncogene Proteins c-mdm2 Retina Retinal Cone Photoreceptor Cells Signal Transduction

Connections (1)

This publication is referenced by other Labnodes entities: