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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
2004-9-6
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pubmed:abstractText |
The type V TGF-beta receptor (TbetaR-V) plays an important role in growth inhibition by IGFBP-3 and TGF-beta in responsive cells. Unexpectedly, TbetaR-V was recently found to be identical to the LRP-1/alpha(2)M receptor; this has disclosed previously unreported growth regulatory functions of LRP-1. Here we demonstrate that, in addition to expressing LRP-1, all cells examined exhibit low affinity but high density acidic pH binding sites for LRP-1 growth regulatory ligands (TGF-beta(1), IGFBP-3, and alpha(2)M(*)). These sites, like LRP-1, are sensitive to receptor-associated protein and calcium depletion but, unlike LRP-1, are also sensitive to chondroitin sulfate and heparin and capable of directly binding ligands, which do not bind to LRP-1. Annexin VI has been identified as a major membrane-associated protein capable of directly binding alpha(2)M(*) at acidic pH. This is evidenced by: 1) structural and Western blot analyses of the protein purified from bovine liver plasma membranes by alpha(2)M(*) affinity column chromatography at acidic pH, and 2) dot blot analysis of the interaction of annexin VI and (125)I-alpha(2)M(*). Cell surface annexin VI is involved in (125)I-TGF-beta(1) and (125)I-alpha(2)M(*) binding to the acidic pH binding sites and (125)I-alpha(2)M(*) binding to LRP-1 at neutral pH as demonstrated by the sensitivity of cells to pretreatment with anti-annexin VI IgG. Cell surface annexin VI is also capable of mediating internalization and degradation of cell surface-bound (125)I-TGF-beta(1) and (125)I-alpha(2)M(*) at pH 6 and of forming ternary complexes with (125)I-alpha(2)M(*) and LRP-1 at neutral pH as demonstrated by co-immunoprecipitation. Trifluoperazine and fluphenazine, which inhibit ligand binding to the acidic pH binding sites, block degradation after internalization of cell surface-bound (125)I-TGF-beta(1) or (125)I-alpha(2)M(*). These results suggest that cell surface annexin VI may function as an acidic pH binding site or receptor and may also function as a co-receptor with LRP-1 at neutral pH.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A6,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chondroitin Sulfates,
http://linkedlifedata.com/resource/pubmed/chemical/Edetic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Fluphenazine,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Lactoferrin,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Sepharose,
http://linkedlifedata.com/resource/pubmed/chemical/Transferrin,
http://linkedlifedata.com/resource/pubmed/chemical/Trifluoperazine,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Macroglobulins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
38736-48
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15226301-Animals,
pubmed-meshheading:15226301-Annexin A6,
pubmed-meshheading:15226301-Binding Sites,
pubmed-meshheading:15226301-Blotting, Western,
pubmed-meshheading:15226301-Calcium,
pubmed-meshheading:15226301-Cattle,
pubmed-meshheading:15226301-Cell Division,
pubmed-meshheading:15226301-Cell Line,
pubmed-meshheading:15226301-Cell Membrane,
pubmed-meshheading:15226301-Chondroitin Sulfates,
pubmed-meshheading:15226301-Dose-Response Relationship, Drug,
pubmed-meshheading:15226301-Edetic Acid,
pubmed-meshheading:15226301-Fibroblasts,
pubmed-meshheading:15226301-Fluphenazine,
pubmed-meshheading:15226301-Heparin,
pubmed-meshheading:15226301-Humans,
pubmed-meshheading:15226301-Hydrogen-Ion Concentration,
pubmed-meshheading:15226301-Immunoglobulin G,
pubmed-meshheading:15226301-Kinetics,
pubmed-meshheading:15226301-Lactoferrin,
pubmed-meshheading:15226301-Ligands,
pubmed-meshheading:15226301-Lipoproteins, LDL,
pubmed-meshheading:15226301-Liver,
pubmed-meshheading:15226301-Low Density Lipoprotein Receptor-Related Protein-1,
pubmed-meshheading:15226301-Mice,
pubmed-meshheading:15226301-Precipitin Tests,
pubmed-meshheading:15226301-Protein Binding,
pubmed-meshheading:15226301-Protein Structure, Tertiary,
pubmed-meshheading:15226301-Sepharose,
pubmed-meshheading:15226301-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:15226301-Transferrin,
pubmed-meshheading:15226301-Trifluoperazine,
pubmed-meshheading:15226301-alpha-Macroglobulins
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pubmed:year |
2004
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pubmed:articleTitle |
Identification and characterization of the acidic pH binding sites for growth regulatory ligands of low density lipoprotein receptor-related protein-1.
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pubmed:affiliation |
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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