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http://purl.uniprot.org/citations/12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12133942http://www.w3.org/2000/01/rdf-schema#comment"G-CSF is a polypeptide growth factor used in treatment following chemotherapy. G-CSF regulates granulopoiesis and acts on its target cells by inducing homodimerization of the G-CSFR, thereby activating intracellular signaling cascades. The G-CSFR encompasses four tyrosine motifs on its cytoplasmic tail that have been shown to recruit a number of regulatory proteins. Suppressor of cytokine signaling 3 (SOCS-3), also referred to as cytokine-inducible Src homolgy 2-containing protein 3, is a member of a recently discovered family of feedback inhibitors that have been shown to inhibit the Janus kinase/STAT pathway. In this study, we demonstrate that human SOCS-3 is rapidly induced by G-CSF in polymorphonuclear neutrophils as well as in the myeloid precursor cell line U937 and that SOCS-3 negatively regulates G-CSFR-mediated STAT activation. Most importantly, we show that SOCS-3 is recruited to the G-CSFR in a phosphorylation-dependent manner and we identify phosphotyrosine (pY)729 as the major recruitment site for SOCS-3. Furthermore, we demonstrate that SOCS-3 directly binds to this pY motif. Surface plasmon resonance analysis reveals a dissociation constant (K(D)) for this interaction of around 2.8 microM. These findings strongly suggest that the recruitment of SOCS-3 to pY729 is important for the modulation of G-CSFR-mediated signal transduction by SOCS-3."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.169.3.1219"xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/author"Heinrich P.C."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/author"Johnston J.A."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/author"Haan S."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/author"Mayr L.M."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/author"Nielsch U."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/author"Hortner M."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/name"J Immunol"xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/pages"1219-1227"xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/title"Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction."xsd:string
http://purl.uniprot.org/citations/12133942http://purl.uniprot.org/core/volume"169"xsd:string
http://purl.uniprot.org/citations/12133942http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12133942
http://purl.uniprot.org/citations/12133942http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12133942
http://purl.uniprot.org/uniprot/#_P09919-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_O60674-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_O14543-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_O15524-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_P07948-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_P08631-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_P29597-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_P23458-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942
http://purl.uniprot.org/uniprot/#_P43405-mappedCitation-12133942http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12133942