PubMed:9153220 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/9153220","sourcedb":"PubMed","sourceid":"9153220","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9153220","text":"Characterization of functional domains within Smad4/DPC4.\nSmad proteins are a family of highly conserved, intracellular proteins that signal cellular responses downstream of transforming growth factor-beta (TGF-beta) family serine/threonine kinase receptors. One of these molecules, Smad4, originally identified as the candidate tumor suppressor gene dpc-4, reconstitutes TGF-beta- and activin-dependent transcriptional responses in Smad4 null cell lines and interacts in a ligand-dependent manner with other Smad family members in both TGF-beta, activin, and bone morphogenetic protein-2/-4 pathways. Here, we used an assay based on the restoration of ligand-dependent transcriptional responses in a Smad4 null cell line to characterize functional domain structures within Smad4. We showed that restoration of TGF-beta-induced transcriptional responses by Smad4 was inhibited by co-transfection with a kinase dead TGF-beta type II receptor and that constitutive activation was blocked with TGF-beta neutralizing antibodies, confirming the essential role of Smad4 in TGF-beta signaling. Using a series of Smad4 mutation, deletion, and Smad1/Smad4 chimera constructs we identified a 47-amino acid deletion within the middle-linker region of Smad4 that is essential for the mediation of signaling responses. In addition, we showed that the NH2-terminal domain of Smad4 augments ligand-dependent activation associated with the middle-linker region, indicating that there is a distinct ligand-response domain within the N terminus of this molecule.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":57},"obj":"Sentence"},{"id":"T2","span":{"begin":58,"end":258},"obj":"Sentence"},{"id":"T3","span":{"begin":259,"end":601},"obj":"Sentence"},{"id":"T4","span":{"begin":602,"end":780},"obj":"Sentence"},{"id":"T5","span":{"begin":781,"end":1086},"obj":"Sentence"},{"id":"T6","span":{"begin":1087,"end":1305},"obj":"Sentence"},{"id":"T7","span":{"begin":1306,"end":1544},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":57},"obj":"Sentence"},{"id":"T2","span":{"begin":58,"end":258},"obj":"Sentence"},{"id":"T3","span":{"begin":259,"end":601},"obj":"Sentence"},{"id":"T4","span":{"begin":602,"end":780},"obj":"Sentence"},{"id":"T5","span":{"begin":781,"end":1086},"obj":"Sentence"},{"id":"T6","span":{"begin":1087,"end":1305},"obj":"Sentence"},{"id":"T7","span":{"begin":1306,"end":1544},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":329,"end":334},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"subj":"T1","pred":"source","obj":"mondo_disease"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":560,"end":564},"obj":"http://purl.obolibrary.org/obo/MAT_0000299"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":560,"end":564},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000299"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":106,"end":119},"obj":"Body_part"},{"id":"T2","span":{"begin":560,"end":564},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0005622"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0001474"},{"id":"A3","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0002481"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":329,"end":334},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002664"},{"subj":"T1","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":439,"end":448},"obj":"Cell"},{"id":"T3","span":{"begin":707,"end":716},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000623"},{"id":"A2","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000825"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000623"},{"id":"A4","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000825"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T3","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#d8ec93","default":true},{"id":"mondo_disease","color":"#e693ec"},{"id":"Glycosmos6-MAT","color":"#93eccc"},{"id":"Anatomy-MAT","color":"#ecb293"},{"id":"Anatomy-UBERON","color":"#9893ec"},{"id":"HP-phenotype","color":"#a8ec93"},{"id":"CL-cell","color":"#ec93c2"}]}]}}