{"doi":"10.3390/ijms21186498","title":"Insight into Molecular Mechanism for Activin A-Induced Bone Morphogenetic Protein Signaling","abstract":"<jats:p>Activins transduce the TGF-β pathway through a heteromeric signaling complex consisting of type I and type II receptors, and activins also inhibit bone morphogenetic protein (BMP) signaling mediated by type I receptor ALK2. Recent studies indicated that activin A cross-activates the BMP pathway through ALK2R206H, a mutation associated with Fibrodysplasia Ossificans Progressiva (FOP). How activin A inhibits ALK2WT-mediated BMP signaling but activates ALK2R206H-mediated BMP signaling is not well understood, and here we offer some insights into its molecular mechanism. We first demonstrated that among four BMP type I receptors, ALK2 is the only subtype able to mediate the activin A-induced BMP signaling upon the dissociation of FKBP12. We further showed that BMP4 does not cross-signal TGF-β pathway upon FKBP12 inhibition. In addition, although the roles of type II receptors in the ligand-independent BMP signaling activated by FOP-associated mutant ALK2 have been reported, their roles in activin A-induced BMP signaling remains unclear. We demonstrated in this study that the known type II BMP receptors contribute to activin A-induced BMP signaling through their kinase activity. Together, the current study provided important mechanistic insights at the molecular level into further understanding physiological and pathophysiological BMP signaling.</jats:p>","journal":"International Journal of Molecular Sciences","year":2020,"id":35695,"datarank":0.4978565517557205,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.15246878780661358,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.15246878780661358,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":8,"citers_with_citation_signal":6,"citers_with_endowment":6,"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":182318,"name":"Wenjuan Jiang","orcid":"0000-0002-6360-3875","position":1,"is_corresponding":false},{"id":182319,"name":"Jerome J. Lacroix","orcid":"0000-0001-5687-0652","position":2,"is_corresponding":false},{"id":17700,"name":"Yun Luo","orcid":"0000-0002-6243-7000","position":3,"is_corresponding":false},{"id":182320,"name":"Jijun Hao","orcid":"0000-0002-6769-9069","position":4,"is_corresponding":false},{"id":182317,"name":"Chen Xie","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"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":"32899497","pmcid":"PMC7555472","openalex_id":"https://openalex.org/W3083067703","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R21NS101384","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM130834","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R21NS101384-02","title":"Biophysical Studies of Non-Invasive Brain Cell Stimulation with Focused Ultrasound"}],"total_grants":3,"fwci":1.0217,"citation_percentile":0.77315191,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":3},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/21/18/6498/pdf","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/21/18/6498/pdf","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/21/18/6498/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms21186498","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32899497","host_type":"repository"},{"url":"https://doaj.org/article/d62c7d69eab34d3c80f5d25db4a24836","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms21186498","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7555472","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7555472","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7555472?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/ijms21186498","host_type":""}],"fields_of_study":["Heterotopic Ossification and Related Conditions","Parathyroid Disorders and Treatments","Medical Imaging and Pathology Studies","Chemistry","Medicine","Biology","0301 basic medicine","03 medical and health sciences","0303 health sciences","Activin Receptors, Type I","Activin Receptors, Type II","Activins","Animals","Bone Morphogenetic Protein Receptors, Type I","Bone Morphogenetic Protein Receptors, Type II","Bone Morphogenetic Proteins","Cell Differentiation","Cell Line","Gene Expression Regulation","HEK293 Cells","Hep G2 Cells","Humans","Mice","Ossification, Heterotopic","Phosphorylation","Signal Transduction","Transforming Growth Factor beta"],"mesh_terms":["Animals","Cell Differentiation","Cell Line","Gene Expression Regulation","Humans","Ossification, Heterotopic","Phosphorylation","Signal Transduction","Transforming Growth Factor beta","Bone Morphogenetic Proteins","Activins","Activin Receptors, Type I","Activin Receptors, Type II","Mice","Bone Morphogenetic Protein Receptors, Type I","Bone Morphogenetic Protein Receptors, Type II","Hep G2 Cells","HEK293 Cells"],"keywords":["BMPR2","Activin receptor","Bone morphogenetic protein","Activin type 2 receptors","ACVR2B","Signal transduction","Bone morphogenetic protein receptor","Cell biology","Receptor","ACVRL1","Biology","Smad2 Protein","Bone morphogenetic protein 2","Bone morphogenetic protein 10","TGF beta signaling pathway","Chemistry","Transforming growth factor beta","Transforming growth factor","Bone morphogenetic protein 7","Endoglin","Genetics","Stem cell","Gene","BMP","Activin A","Fkbp12","Fibrodysplasia Ossificans Progressiva","Alk2","Activin Receptors, Type II","Bone Morphogenetic Protein Receptors, Type II","Article","Cell Line","Mice","Animals","Humans","Phosphorylation","Bone Morphogenetic Protein Receptors, Type I","Ossification, Heterotopic","Cell Differentiation","Hep G2 Cells","Activins","HEK293 Cells","Gene Expression Regulation","Bone Morphogenetic Proteins","Activin Receptors, Type I"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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