{"doi":"10.1101/2020.05.14.094961","title":"Multiple domains in ARHGAP36 regulate PKA degradation and Gli activation","abstract":"ABSTRACT ARHGAP36 is a Rho GTPase-activating protein (GAP) family member that contributes to spinal cord development and tumorigenesis. This multidomain protein is composed of splicing-dependent N-terminal sequences, the GAP-like region, and a unique C-terminal domain, and an N-terminal arginine-rich region has been shown to suppress protein kinase A (PKA) and activate Gli transcription factors. To understand how these structural elements act in concert, we have mapped the ARHGAP36 structure-activity landscape with domain- and amino-acid-level resolution. ARHGAP36-mediated Gli activation can be repressed by N-terminal sequences that regulate subcellular ARHGAP36 localization and PKA targeting. The GAP-like and C-terminal domains counteract this autoinhibitory mechanism and promote ARHGAP36 trafficking to the plasma membrane and primary cilium, respectively. The GAP-like domain may also conditionally suppress the arginine-rich region, and it modulates ARHGAP36 binding to the prolyl oligopeptidase-like protein PREPL and the E3 ubiquitin ligase PRAJA2. These domain-dependent activities provide a potential means for tissue-specific ARHGAP36 functions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":129672,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":74193,"name":"Takamasa Kudo","orcid":"0000-0002-9709-5549","position":1,"is_corresponding":false},{"id":292504,"name":"Nancie A. Mooney","orcid":"0000-0001-5930-447X","position":2,"is_corresponding":false},{"id":581318,"name":"Jun Ni","orcid":"0000-0002-4479-8494","position":3,"is_corresponding":false},{"id":107286,"name":"János Demeter","orcid":"0000-0002-7301-8055","position":4,"is_corresponding":false},{"id":84075,"name":"Peter K. Jackson","orcid":"0000-0002-1742-2539","position":5,"is_corresponding":false},{"id":297986,"name":"James Chen","orcid":"0000-0002-9220-8436","position":6,"is_corresponding":false},{"id":581317,"name":"Patricia R. Nano","orcid":"0000-0002-5507-2656","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:49.682497Z","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":[]}