{"doi":"10.3390/ijms26020552","title":"An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs","abstract":"<jats:p>G protein-coupled receptors (GPCRs), critical for cellular communication and signaling, represent the largest cell surface protein family and play important roles in numerous pathophysiological processes. Consequently, GPCRs have become a primary focus in drug discovery efforts. Beyond their traditional G protein-dependent signaling pathways, GPCRs are also capable of activating alternative signaling mechanisms, including G protein-independent signaling, biased signaling, and signaling crosstalk. A particularly novel signaling mode employed by these receptors is GPCR transactivation, which enables cross-communication between GPCRs and other receptor types. Intriguingly, GPCR transactivation by distinct GPCRs has also been identified. In this review, I provide an overview of the known GPCR transactivation mechanisms and explore recently uncovered GPCR transactivation mediated by adhesion-class GPCRs (aGPCRs). These aGPCR-GPCR transactivation processes regulate unique cell type-specific functions, offering an exciting opportunity to develop therapies that precisely modulate specific GPCR-mediated biological effects.</jats:p>","journal":"International Journal of Molecular Sciences","year":2025,"id":677229,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1769489,"name":"Hsi-Hsien Lin","orcid":"0000-0003-2798-3855","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs","abstract":"<jats:p>G protein-coupled receptors (GPCRs), critical for cellular communication and signaling, represent the largest cell surface protein family and play important roles in numerous pathophysiological processes. Consequently, GPCRs have become a primary focus in drug discovery efforts. Beyond their traditional G protein-dependent signaling pathways, GPCRs are also capable of activating alternative signaling mechanisms, including G protein-independent signaling, biased signaling, and signaling crosstalk. A particularly novel signaling mode employed by these receptors is GPCR transactivation, which enables cross-communication between GPCRs and other receptor types. Intriguingly, GPCR transactivation by distinct GPCRs has also been identified. In this review, I provide an overview of the known GPCR transactivation mechanisms and explore recently uncovered GPCR transactivation mediated by adhesion-class GPCRs (aGPCRs). These aGPCR-GPCR transactivation processes regulate unique cell type-specific functions, offering an exciting opportunity to develop therapies that precisely modulate specific GPCR-mediated biological effects.</jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39859266","pmcid":"PMC11765499","openalex_id":"https://openalex.org/W4406245281","authors":[],"funders":[{"funder_name":"Chang Gung Memorial Hospital, Taiwan","grant_id":"CMRPD1M0033","title":null},{"funder_name":"Chang Gung Memorial Hospital, Taiwan","grant_id":"CMRPD1M0323","title":null},{"funder_name":"Chang Gung Memorial Hospital, Taiwan","grant_id":"NSTC-113-2918-182-001","title":null},{"funder_name":"Chang Gung Memorial Hospital, Taiwan","grant_id":"NSTC-113-2320-B-182-009","title":null},{"funder_name":"National Science and Technology Council","grant_id":"NSTC-113-2918-182-001, NSTC-113-2320-B-182-009","title":null},{"funder_name":"Linkou Chang Gung Memorial Hospital","grant_id":"CMRPD1M0033, CMRPD1M0323","title":null}],"total_grants":6,"fwci":3.4656,"citation_percentile":0.92443932,"influential_citations":0,"citation_trend":[{"year":2025,"count":5},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/26/2/552/pdf","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/26/2/552/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms26020552","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39859266","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11765499","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11765499/pdf/ijms-26-00552.pdf","host_type":"repository"},{"url":"https://www.mdpi.com/1422-0067/26/2/552/pdf?version=1736502556","host_type":"Unpaywall"},{"url":"https://europepmc.org/articles/PMC11765499","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11765499?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Receptor Mechanisms and Signaling","Neuropeptides and Animal Physiology","Monoclonal and Polyclonal Antibodies Research"],"mesh_terms":["Animals","Cell Adhesion","Humans","Signal Transduction","Transcriptional Activation","Receptors, G-Protein-Coupled"],"keywords":["G protein-coupled receptor","Transactivation","Biology","Signal transduction","Crosstalk","Cell biology","Computational biology","Genetics","Transcription factor","Gene","Protease","Receptor","Signaling","Adhesion Gpcr","Gpcr Transactivation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T03:50:59.647777Z","pmid":null,"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":[]}