| Ling TY |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=6.355 ------>paper_class3=2 ------>paper_class2=1 ------>vol=279 ------>confirm_bywho=None ------>insert_bywho=rita1204 ------>Jurnal_Rank=11.9 ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=1 ------>paper_class2Letter=None ------>page2=38748 ------>medlineContent= ------>unit=E0103 ------>insert_date=20040921 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=6 ------>ISSN= ------>authors_c=None ------>score=500 ------>journal_name=J. Biol. Chem. ------>paper_name=Identification and Characterization of the Acidic pH Binding Sites for Growth Regulatory Ligands of Low Density Lipoprotein Receptor-related protein-1 ------>confirm_date=None ------>tch_id=090143 ------>pmid=15226301 ------>page1=38736 ------>fullAbstract=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. ------>tmu_sno=None ------>sno=9707 ------>authors2=Chen CL ------>authors3=Huang YH ------>authors4=Liu IH ------>authors5=Huang SS ------>authors6=Huang JS ------>authors6_c=None ------>authors=Ling TY ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=0 ------>updateTitle=Identification and characterization of the acidic pH binding sites for growth regulatory ligands of low density lipoprotein receptor-related protein-1. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=37 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2004 ------>submit_flag=None ------>publish_month=9 |