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http://purl.uniprot.org/citations/15171717http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15171717http://www.w3.org/2000/01/rdf-schema#comment"The neoplastic production of the insulin-like growth factor binding protein (IGFBP)-2 often correlates with tumor malignancy and aggressiveness. Since IGFBP-2 contains an RGD motif in its C-terminus, it was hypothesized that this protein may act independently of IGF on tumor cells through integrins. To investigate this, integrin binding, intracellular signaling and the impact of IGFBP-2 on cell adhesion and proliferation were examined in two tumor cell lines. In tracer displacement studies, up to 30% of the added (125)I-hIGFBP-2 specifically bound to the cells. Bound (125)I-hIGFBP-2 was reversibly displaced by IGFBP-2, IGFBP-1 and RGD-(Gly-Arg-Asp)-containing peptides, but not by IGFBP-3, -4, -5, -6 and RGE-(Gly-Arg-Glu)-containing peptides. Blocking with antibodies directed against different integrins and with fibronectin demonstrated that IGFBP-2 cell surface binding is specific for alpha5beta1-integrin. Incubation of IGFBP-2 with equimolar quantities of IGF-I and IGF-II annihilated RGD-specific binding. IGFBP-2 binding at the cell surface led to dephosphorylation of the focal adhesion-kinase (FAK) of up to 37% (P<0.01), and of the p42/44 MAP-kinases of up to 40% (P<0.01). In addition, IGFBP-2 promoted de-adhesion of the cells dose-dependently by up to 30% (P<0.05), and reduced proliferation by 24% (P<0.01). Since one of the cell lines used does not express a functional IGF-I receptor, these data demonstrate that IGFBP-2 can act in an IGF-independent manner, at least in part by an interaction with alpha5beta1-integrin."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.org/dc/terms/identifier"doi:10.1677/jme.0.0320859"xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/author"Elmlinger M.W."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/author"Ranke M.B."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/author"Schutt B.S."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/author"Langkamp M."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/author"Rauschnabel U."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/name"J Mol Endocrinol"xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/pages"859-868"xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/title"Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells."xsd:string
http://purl.uniprot.org/citations/15171717http://purl.uniprot.org/core/volume"32"xsd:string
http://purl.uniprot.org/citations/15171717http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15171717
http://purl.uniprot.org/citations/15171717http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15171717
http://purl.uniprot.org/uniprot/#_C9JMY1-mappedCitation-15171717http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15171717
http://purl.uniprot.org/uniprot/#_P18065-mappedCitation-15171717http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15171717
http://purl.uniprot.org/uniprot/#_Q59FF1-mappedCitation-15171717http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15171717
http://purl.uniprot.org/uniprot/C9JMY1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15171717
http://purl.uniprot.org/uniprot/P18065http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15171717
http://purl.uniprot.org/uniprot/Q59FF1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15171717