{"doi":"10.17615/cdz9-a259","title":"Deletion of the Protein Kinase A/Protein Kinase G Target SMTNL1 Promotes an Exercise-adapted Phenotype in Vascular Smooth Muscle","abstract":"In vivo protein kinases A and G (PKA and PKG) coordinately phosphorylate a broad range of substrates to mediate their various physiological effects. The functions of many of these substrates have yet to be defined genetically. Herein we show a role for smoothelin-like protein 1 (SMTNL1), a novel in vivo target of PKG/PKA, in mediating vascular adaptations to exercise. Aortas from smtnl1-/- mice exhibited strikingly enhanced vasorelaxation before exercise, similar in extent to that achieved after endurance training of wild-type littermates. Additionally, contractile responses to α-adrenergic agonists were greatly attenuated. Immunological studies showed SMTNL1 is expressed in smooth muscle and type 2a striated muscle fibers. Consistent with a role in adaptations to exercise, smtnl1-/- mice also exhibited increased type 2a fibers before training and better performance after forced endurance training compared smtnl1+/+ mice. Furthermore, exercise was found to reduce expression of SMTNL1, particularly in female mice. In both muscle types, SMTNL1 is phosphorylated at Ser-301 in response to adrenergic signals. In vitro SMTNL1 suppresses myosin phosphatase activity through a substrate-directed effect, which is relieved by Ser-301 phosphorylation. Our findings suggest roles for SMTNL1 in cGMP/cAMP-mediated adaptations to exercise through mechanisms involving direct modulation of contractile activity.","journal":"UNC Libraries","year":2020,"id":144402,"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":0.9474,"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":593693,"name":"Zhen Yan","orcid":"0000-0002-6807-2428","position":1,"is_corresponding":false},{"id":548713,"name":"Avril V. Somlyo","orcid":"0000-0002-9997-4897","position":2,"is_corresponding":false},{"id":431978,"name":"Ronald L. Neppl","orcid":"0000-0003-1497-6058","position":3,"is_corresponding":false},{"id":540278,"name":"Randy Thresher","orcid":null,"position":4,"is_corresponding":false},{"id":290796,"name":"Timothy Haystead","orcid":"0000-0001-7274-1519","position":5,"is_corresponding":false},{"id":612892,"name":"Timothy P. Gavin","orcid":"0000-0002-4616-8373","position":6,"is_corresponding":false},{"id":485342,"name":"Sara Miller","orcid":"0000-0002-9441-0101","position":7,"is_corresponding":false},{"id":612893,"name":"Christopher N. Fortner","orcid":"0000-0003-4171-3827","position":8,"is_corresponding":false},{"id":268691,"name":"Ping Li","orcid":"0000-0002-4549-9517","position":9,"is_corresponding":false},{"id":613486,"name":"Jean Claude Perriard","orcid":null,"position":10,"is_corresponding":false},{"id":542887,"name":"Thomas M. Coffman","orcid":"0000-0002-8433-1629","position":11,"is_corresponding":false},{"id":612894,"name":"Beáta Lontay","orcid":"0000-0002-2545-8275","position":12,"is_corresponding":false},{"id":612895,"name":"Takayuki Akimoto","orcid":"0000-0002-8874-7779","position":13,"is_corresponding":false},{"id":612896,"name":"Anne A. Wooldridge","orcid":"0000-0003-1811-982X","position":14,"is_corresponding":false},{"id":612897,"name":"Ashley Kwon","orcid":"0000-0001-9635-7482","position":15,"is_corresponding":false},{"id":612898,"name":"Michael Datto","orcid":"0000-0002-9777-383X","position":16,"is_corresponding":false},{"id":304736,"name":"Shiliang Wang","orcid":"0000-0001-9709-6587","position":17,"is_corresponding":false},{"id":55105,"name":"Robert C. Hickner","orcid":"0000-0002-2683-1617","position":18,"is_corresponding":false},{"id":543659,"name":"Carie Facemire","orcid":null,"position":19,"is_corresponding":false},{"id":598048,"name":"E.C. McCook","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:45.339291Z","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":[]}