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GlycoBiology-FMA

uniprot-human

{"project":"uniprot-human","denotations":[{"id":"T1","span":{"begin":18,"end":25},"obj":"http://www.uniprot.org/uniprot/P01308"},{"id":"T2","span":{"begin":31,"end":46},"obj":"http://www.uniprot.org/uniprot/P13385"},{"id":"T3","span":{"begin":31,"end":46},"obj":"http://www.uniprot.org/uniprot/Q99684"},{"id":"T4","span":{"begin":31,"end":46},"obj":"http://www.uniprot.org/uniprot/P05230"},{"id":"T5","span":{"begin":31,"end":46},"obj":"http://www.uniprot.org/uniprot/P28069"},{"id":"T6","span":{"begin":31,"end":55},"obj":"http://www.uniprot.org/uniprot/Q9UDF2"},{"id":"T7","span":{"begin":38,"end":55},"obj":"http://www.uniprot.org/uniprot/Q5T3J3"},{"id":"T8","span":{"begin":449,"end":466},"obj":"http://www.uniprot.org/uniprot/P03372"},{"id":"T9","span":{"begin":476,"end":494},"obj":"http://www.uniprot.org/uniprot/Q8IZY5"},{"id":"T10","span":{"begin":550,"end":552},"obj":"http://www.uniprot.org/uniprot/O94907"},{"id":"T11","span":{"begin":957,"end":959},"obj":"http://www.uniprot.org/uniprot/O94907"},{"id":"T12","span":{"begin":550,"end":552},"obj":"http://www.uniprot.org/uniprot/Q92952"},{"id":"T13","span":{"begin":957,"end":959},"obj":"http://www.uniprot.org/uniprot/Q92952"},{"id":"T14","span":{"begin":553,"end":556},"obj":"http://www.uniprot.org/uniprot/P61006"},{"id":"T15","span":{"begin":960,"end":963},"obj":"http://www.uniprot.org/uniprot/P61006"},{"id":"T16","span":{"begin":1307,"end":1320},"obj":"http://www.uniprot.org/uniprot/P08833"},{"id":"T17","span":{"begin":1659,"end":1675},"obj":"http://www.uniprot.org/uniprot/P08833"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

uniprot-mouse

{"project":"uniprot-mouse","denotations":[{"id":"T1","span":{"begin":449,"end":466},"obj":"http://www.uniprot.org/uniprot/P19785"},{"id":"T2","span":{"begin":1307,"end":1320},"obj":"http://www.uniprot.org/uniprot/P47876"},{"id":"T3","span":{"begin":1659,"end":1675},"obj":"http://www.uniprot.org/uniprot/P47876"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

GlycoBiology-NCBITAXON

GO-BP

{"project":"GO-BP","denotations":[{"id":"T1","span":{"begin":31,"end":37},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T2","span":{"begin":1603,"end":1609},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T3","span":{"begin":1832,"end":1838},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T4","span":{"begin":381,"end":390},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T5","span":{"begin":900,"end":909},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T6","span":{"begin":995,"end":1008},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T7","span":{"begin":1148,"end":1161},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T8","span":{"begin":1357,"end":1381},"obj":"http://purl.obolibrary.org/obo/GO_0098737"},{"id":"T9","span":{"begin":1357,"end":1381},"obj":"http://purl.obolibrary.org/obo/GO_0072661"},{"id":"T10","span":{"begin":1357,"end":1381},"obj":"http://purl.obolibrary.org/obo/GO_0072659"},{"id":"T11","span":{"begin":1827,"end":1838},"obj":"http://purl.obolibrary.org/obo/GO_0016049"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

GO-MF

{"project":"GO-MF","denotations":[{"id":"T1","span":{"begin":728,"end":734},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T2","span":{"begin":735,"end":742},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T3","span":{"begin":1313,"end":1320},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T4","span":{"begin":1659,"end":1666},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T5","span":{"begin":1938,"end":1945},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T6","span":{"begin":735,"end":742},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T7","span":{"begin":1313,"end":1320},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T8","span":{"begin":1659,"end":1666},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T9","span":{"begin":1938,"end":1945},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T10","span":{"begin":735,"end":742},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T11","span":{"begin":1313,"end":1320},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T12","span":{"begin":1659,"end":1666},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T13","span":{"begin":1938,"end":1945},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T14","span":{"begin":735,"end":742},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T15","span":{"begin":1313,"end":1320},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T16","span":{"begin":1659,"end":1666},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T17","span":{"begin":1938,"end":1945},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T18","span":{"begin":1625,"end":1633},"obj":"http://purl.obolibrary.org/obo/GO_0003823"},{"id":"T19","span":{"begin":1659,"end":1673},"obj":"http://purl.obolibrary.org/obo/GO_0005520"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

GO-CC

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T1","span":{"begin":68,"end":74},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"T2","span":{"begin":329,"end":335},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"T3","span":{"begin":476,"end":482},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"T4","span":{"begin":1878,"end":1884},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

EDAM-topics

{"project":"EDAM-topics","denotations":[{"id":"T1","span":{"begin":75,"end":81},"obj":"http://edamontology.org/topic_2640"},{"id":"T2","span":{"begin":208,"end":215},"obj":"http://edamontology.org/topic_0602"},{"id":"T3","span":{"begin":225,"end":230},"obj":"http://edamontology.org/topic_3678"},{"id":"T4","span":{"begin":336,"end":342},"obj":"http://edamontology.org/topic_2640"},{"id":"T5","span":{"begin":483,"end":489},"obj":"http://edamontology.org/topic_2640"},{"id":"T6","span":{"begin":1364,"end":1381},"obj":"http://edamontology.org/topic_0820"},{"id":"T7","span":{"begin":1373,"end":1381},"obj":"http://edamontology.org/topic_0078"},{"id":"T8","span":{"begin":1885,"end":1891},"obj":"http://edamontology.org/topic_2640"},{"id":"T9","span":{"begin":2122,"end":2129},"obj":"http://edamontology.org/topic_0602"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

EDAM-DFO

{"project":"EDAM-DFO","denotations":[{"id":"T1","span":{"begin":208,"end":215},"obj":"http://edamontology.org/data_2600"},{"id":"T2","span":{"begin":515,"end":525},"obj":"http://edamontology.org/operation_2424"},{"id":"T3","span":{"begin":772,"end":781},"obj":"http://edamontology.org/data_3108"},{"id":"T4","span":{"begin":852,"end":863},"obj":"http://edamontology.org/operation_2246"},{"id":"T5","span":{"begin":1217,"end":1227},"obj":"http://edamontology.org/operation_3465"},{"id":"T6","span":{"begin":1321,"end":1329},"obj":"http://edamontology.org/operation_2945"},{"id":"T7","span":{"begin":1373,"end":1381},"obj":"http://edamontology.org/data_1467"},{"id":"T8","span":{"begin":1373,"end":1381},"obj":"http://edamontology.org/format_1208"},{"id":"T9","span":{"begin":1514,"end":1520},"obj":"http://edamontology.org/operation_3435"},{"id":"T10","span":{"begin":1951,"end":1955},"obj":"http://edamontology.org/data_0006"},{"id":"T11","span":{"begin":2122,"end":2129},"obj":"http://edamontology.org/data_2600"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

performance-test

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":68,"end":74},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":329,"end":335},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":476,"end":482},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":1878,"end":1884},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":329,"end":342},"obj":"HP_0003002"},{"id":"T2","span":{"begin":329,"end":342},"obj":"HP_0100013"},{"id":"T3","span":{"begin":336,"end":342},"obj":"HP_0002664"},{"id":"T4","span":{"begin":476,"end":489},"obj":"HP_0003002"},{"id":"T5","span":{"begin":476,"end":489},"obj":"HP_0100013"},{"id":"T6","span":{"begin":483,"end":489},"obj":"HP_0002664"},{"id":"T7","span":{"begin":531,"end":539},"obj":"HP_0002861"},{"id":"T8","span":{"begin":1065,"end":1073},"obj":"HP_0002861"},{"id":"T9","span":{"begin":1878,"end":1891},"obj":"HP_0003002"},{"id":"T10","span":{"begin":1878,"end":1891},"obj":"HP_0100013"},{"id":"T11","span":{"begin":1885,"end":1891},"obj":"HP_0002664"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

mondo_disease

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":68,"end":81},"obj":"Disease"},{"id":"T2","span":{"begin":329,"end":342},"obj":"Disease"},{"id":"T3","span":{"begin":449,"end":489},"obj":"Disease"},{"id":"T4","span":{"begin":531,"end":539},"obj":"Disease"},{"id":"T5","span":{"begin":1065,"end":1073},"obj":"Disease"},{"id":"T6","span":{"begin":1878,"end":1891},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0006513"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005105"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005105"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0007254"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

HP-phenotype

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":68,"end":81},"obj":"Phenotype"},{"id":"T2","span":{"begin":329,"end":342},"obj":"Phenotype"},{"id":"T3","span":{"begin":476,"end":489},"obj":"Phenotype"},{"id":"T4","span":{"begin":531,"end":539},"obj":"Phenotype"},{"id":"T5","span":{"begin":1065,"end":1073},"obj":"Phenotype"},{"id":"T6","span":{"begin":1878,"end":1891},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0003002"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0003002"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0003002"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0002861"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0002861"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"HP:0003002"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}

Anatomy-UBERON

CL-cell

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":75,"end":87},"obj":"Cell"},{"id":"T2","span":{"begin":336,"end":348},"obj":"Cell"},{"id":"T3","span":{"begin":483,"end":494},"obj":"Cell"},{"id":"T4","span":{"begin":1885,"end":1897},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0001064"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0001064"},{"id":"A3","pred":"cl_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CL:0001064"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0001064"}],"text":"Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway.\nIn this study we provide evidence that the low expression of IGF-1R at the cell surface of estrogen-independent breast cancer cells is due to a low rate of de novo synthesis of dolichyl phosphate. The analyses were performed on the estrogen receptor-negative breast cancer cell line MDA231 and, in comparison, the melanoma cell line SK-MEL-2, which expresses a high number of plasma membrane-bound IGF-1R. Whereas the MDA231 cells had little or no surface expression of IGF-1R, they expressed functional (i.e., ligand-binding) intracellular receptors. By measuring the incorporation of [3H]mevalonate into dolichyl phosphate, we could demonstrate that the rate of dolichyl phosphate synthesis was considerably lower in MDA231 cells than in SK-MEL-2 cells. Furthermore, N-linked glycosylation of the alpha-subunit of IGF-1R was 8-fold higher in the melanoma cells. Following addition of dolichyl phosphate to MDA231 cells, N-linked glycosylation of IGF-1R was drastically increased, which in turn was correlated to a substantial translocation of IGF-1R to the plasma membrane, as assayed by IGF-1 binding analysis and by Western blotting of plasma membrane proteins. The dolichyl phosphate-stimulated receptors were proven to be biochemically active since they exhibited autophosphorylation. Under normal conditions MDA231 cells, expressing very few IGF-1R at the cell surface, were not growth-arrested by an antibody (alphaIR-3) blocking the binding of IGF-1 to IGF-1R. However, after treatment with dolichyl phosphate, leading to a high cell surface expression of IGF-1R, alphaIR-3 efficiently blocked MDA231 cell growth. Taken together with the fact that the breast cancer cells produce IGF-1 and exhibit intracellular binding, our data suggest that the level of de novo -synthesized dolichyl phosphate may be critical for whether the cells will use an intracellular or an extracellular autocrine IGF-1 pathway."}