{"doi":"10.3390/ijms23158679","title":"Short Arrestin-3-Derived Peptides Activate JNK3 in Cells","abstract":"Arrestins were first discovered as suppressors of G protein-mediated signaling by G protein-coupled receptors. It was later demonstrated that arrestins also initiate several signaling branches, including mitogen-activated protein kinase cascades. Arrestin-3-dependent activation of the JNK family can be recapitulated with peptide fragments, which are monofunctional elements distilled from this multi-functional arrestin protein. Here, we use maltose-binding protein fusions of arrestin-3-derived peptides to identify arrestin elements that bind kinases of the ASK1-MKK4/7-JNK3 cascade and the shortest peptide facilitating JNK signaling. We identified a 16-residue arrestin-3-derived peptide expressed as a Venus fusion that leads to activation of JNK3α2 in cells. The strength of the binding to the kinases does not correlate with peptide activity. The ASK1-MKK4/7-JNK3 cascade has been implicated in neuronal apoptosis. While inhibitors of MAP kinases exist, short peptides are the first small molecule tools that can activate MAP kinases.","journal":"International Journal of Molecular Sciences","year":2022,"id":260054,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":768122,"name":"Tamer S. Kaoud","orcid":"0000-0003-1298-8725","position":1,"is_corresponding":false},{"id":246973,"name":"Henriette Stoy","orcid":"0000-0002-2943-414X","position":2,"is_corresponding":false},{"id":478346,"name":"Xuanzhi Zhan","orcid":null,"position":3,"is_corresponding":false},{"id":669691,"name":"Qiuyan Chen","orcid":"0000-0001-9637-4995","position":4,"is_corresponding":false},{"id":292931,"name":"Kevin N. Dalby","orcid":"0000-0001-9272-5129","position":5,"is_corresponding":false},{"id":315280,"name":"T.M. Iverson","orcid":"0000-0001-8816-6352","position":6,"is_corresponding":false},{"id":271822,"name":"Vsevolod V. Gurevich","orcid":"0000-0002-3950-5351","position":7,"is_corresponding":false},{"id":271823,"name":"Eugenia V. Gurevich","orcid":"0000-0002-0563-8295","position":8,"is_corresponding":false},{"id":573801,"name":"Nicole A. Perry","orcid":"0000-0003-3130-3023","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:26:03.189798Z","pmid":"35955810","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}