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http://purl.uniprot.org/citations/12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12393416http://www.w3.org/2000/01/rdf-schema#comment"We have investigated the role of Smad family proteins, known to be important cytoplasmic mediators of signals from the transforming growth factor-beta (TGF-beta) receptor serine/threonine kinases, in TGF-beta-dependent differentiation of hematopoietic cells, using as a model the human promyelocytic leukemia cell line, HL-60. TGF-beta-dependent differentiation of these cells to monocytes, but not retinoic acid-dependent differentiation to granulocytes, was accompanied by rapid phosphorylation and nuclear translocation of Smad2 and Smad3. Vitamin D(3) also induced phosphorylation of Smad2/3 and monocytic differentiation; however the effects were indirect, dependent on its ability to induce expression of TGF-beta1. Simultaneous treatment of these cells with TGF-beta1 and all-trans-retinoic acid (ATRA), which leads to almost equal numbers of granulocytes and monocytes, significantly reduced the level of phospho-Smad2/3 and its nuclear accumulation, compared with that in cells treated with TGF-beta1 alone. TGF-beta1 and ATRA activate P42/44 mitogen-activated protein (MAP) kinase with nearly identical kinetics, ruling out its involvement in these effects on Smad phosphorylation. Addition of the inhibitor-of-protein serine/threonine phosphatases, okadaic acid, blocks the ATRA-mediated reduction in TGF-beta-induced phospho-Smad2 and shifts the differentiation toward monocytic end points. In HL-60R mutant cells, which harbor a defective retinoic acid receptor-alpha (RAR-alpha), ATRA is unable to reduce levels of TGF-beta-induced phospho-Smad2/3, coincident with its inability to differentiate these cells along granulocytic pathways. Together, these data suggest a new level of cross-talk between ATRA and TGF-beta, whereby a putative RAR-alpha-dependent phosphatase activity limits the levels of phospho-Smad2/3 induced by TGF-beta, ultimately reducing the levels of nuclear Smad complexes mediating the TGF-beta-dependent differentiation of the cells to monocytic end points."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.org/dc/terms/identifier"doi:10.1182/blood-2002-05-1549"xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Cao Z."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Roberts A.B."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Parks W.T."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Wurthner J.U."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Ruscetti F.W."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Letterio J.J."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Flanders K.C."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Lyakh L.A."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/author"Bertolette D."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/name"Blood"xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/pages"498-507"xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/title"Levels of phospho-Smad2/3 are sensors of the interplay between effects of TGF-beta and retinoic acid on monocytic and granulocytic differentiation of HL-60 cells."xsd:string
http://purl.uniprot.org/citations/12393416http://purl.uniprot.org/core/volume"101"xsd:string
http://purl.uniprot.org/citations/12393416http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12393416
http://purl.uniprot.org/citations/12393416http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12393416
http://purl.uniprot.org/uniprot/#_A0A078BBI5-mappedCitation-12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393416
http://purl.uniprot.org/uniprot/#_A0A078BC11-mappedCitation-12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393416
http://purl.uniprot.org/uniprot/#_A0A078BCJ0-mappedCitation-12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393416
http://purl.uniprot.org/uniprot/#_A0A078BFK3-mappedCitation-12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393416
http://purl.uniprot.org/uniprot/#_A0A078BCH8-mappedCitation-12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393416
http://purl.uniprot.org/uniprot/#_A0A510GAF6-mappedCitation-12393416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393416