PubMed:8288587 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/8288587","sourcedb":"PubMed","sourceid":"8288587","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/8288587","text":"Protein kinase C-mediated serine phosphorylation directly activates Raf-1 in murine hematopoietic cells.\nWe have previously found that Raf-1, which is activated by hematopoietic growth factors in association with phosphorylation, is required for hematopoietic cell proliferation. Recently, 12-O-tetradecanoylphorbol 13-acetate has been found to mediate Raf-1 phosphorylation, suggesting that protein kinase C (PKC) may be involved in the Raf-1 activation mechanism(s). Since PKC can be activated by hematopoietic growth factors, it was investigated as a potential \"Raf-1 kinase-kinase.\" Results demonstrate that bryostatin 1, a pharmacologic activator of PKC, induces activation of Raf-1 in FDC-P1 cells. PKC inhibitors H7 and staurosporine block both bryostatin 1- and interleukin-3-mediated Raf-1 phosphorylation and FDC-P1 cell proliferation. Additionally, an antisense c-raf oligodeoxyribonucleotide specifically inhibits bryostatin 1-mediated proliferation, indicating a necessary role for Raf-1 in PKC signaling. Purified PKC can phosphorylate Raf-1 serine residues to high stoichiometry in vitro. Comparative phosphopeptide maps localize two PKC phosphorylation sites to Raf-1 phosphopeptides isolated from hematopoietic growth factor- or bryostatin 1-stimulated cells. The sites of PKC-mediated Raf-1 phosphorylation are deduced to be Ser497 and Ser619. Furthermore, PKC-mediated serine phosphorylation is sufficient to activate the enzymatic function of Raf-1 in vitro. These findings demonstrate that activated PKC can promote hematopoietic cell growth by regulating the enzymatic activity of Raf-1 through direct serine phosphorylation.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":104},"obj":"Sentence"},{"id":"T2","span":{"begin":105,"end":279},"obj":"Sentence"},{"id":"T3","span":{"begin":280,"end":468},"obj":"Sentence"},{"id":"T4","span":{"begin":469,"end":704},"obj":"Sentence"},{"id":"T5","span":{"begin":705,"end":845},"obj":"Sentence"},{"id":"T6","span":{"begin":846,"end":1018},"obj":"Sentence"},{"id":"T7","span":{"begin":1019,"end":1103},"obj":"Sentence"},{"id":"T8","span":{"begin":1104,"end":1276},"obj":"Sentence"},{"id":"T9","span":{"begin":1277,"end":1361},"obj":"Sentence"},{"id":"T10","span":{"begin":1362,"end":1478},"obj":"Sentence"},{"id":"T11","span":{"begin":1479,"end":1647},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":104},"obj":"Sentence"},{"id":"T2","span":{"begin":105,"end":279},"obj":"Sentence"},{"id":"T3","span":{"begin":280,"end":468},"obj":"Sentence"},{"id":"T4","span":{"begin":469,"end":704},"obj":"Sentence"},{"id":"T5","span":{"begin":705,"end":845},"obj":"Sentence"},{"id":"T6","span":{"begin":846,"end":1018},"obj":"Sentence"},{"id":"T7","span":{"begin":1019,"end":1103},"obj":"Sentence"},{"id":"T8","span":{"begin":1104,"end":1276},"obj":"Sentence"},{"id":"T9","span":{"begin":1277,"end":1361},"obj":"Sentence"},{"id":"T10","span":{"begin":1362,"end":1478},"obj":"Sentence"},{"id":"T11","span":{"begin":1479,"end":1647},"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":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","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"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":84,"end":103},"obj":"Body_part"},{"id":"T2","span":{"begin":246,"end":264},"obj":"Body_part"},{"id":"T3","span":{"begin":1537,"end":1555},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000988"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000988"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL_0000988"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T3","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":84,"end":103},"obj":"Cell"},{"id":"T2","span":{"begin":246,"end":264},"obj":"Cell"},{"id":"T3","span":{"begin":1537,"end":1555},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000988"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000988"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0000988"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T2","pred":"source","obj":"CL-cell"},{"subj":"T3","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#93bbec","default":true},{"id":"Anatomy-UBERON","color":"#d5ec93"},{"id":"CL-cell","color":"#e893ec"}]}]}}