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TISSUE PLASMINOGEN ACTIVATOR BINDING TO ANNEXIN II TAIL DOMAIN DIRECT MODULATION

TISSUE PLASMINOGEN ACTIVATOR BINDING TO ANNEXIN II TAIL DOMAIN DIRECT MODULATION
组织纤溶酶原激活剂与膜联蛋白 II 尾部结构域的结合直接调节
批准号:
6118263
负责人:
KATHERINE AMBERSON HAJJAR
金额:
$0.17万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-12-10 至 1999-11-30

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中文摘要
翻译
组织纤溶酶原激活剂通过
英文摘要
Tissue plasminogen activator binds to endothelial cells via the calcium-regulated phospholipid-binding protein annexin II, an interaction that is inhibited by the prothrombotic amino acid homocysteine. We sought to identify the tissue plasminogen activator binding domain of annexin II and to determine the mechanism of its modulation by homocysteine. Tissue plasminogen activator binding to immobilized annexin II was inhibited by intact fluid phase annexin II but not by its "core" fragment (residues 25-339). Two overlapping "tail" peptides specifically blocked 65-75% of binding. Localization of the tissue plasminogen activator binding domain was confirmed upon specific inhibition by the hexapeptide LCKLSL (residues 7-12). Expressed C9G annexin II protein failed to support tissue plasminogen activator binding, while binding to C133G, C262G, and C335G was equivalent to that of wild type annexin II. Upon exposure to homocysteine, annexin II underwent a 135 +/- 4-Da increase in mass localizing specifically to Cys9 and a 60-66% loss in tissue plasminogen activator-binding capacity. Upon treatment of cultured endothelial cells with [35S]homocysteine, the dithiothreitol-sensitive label was recovered by immunoprecipitation with anti-annexin II IgG. These data provide a potential mechanism for the prothrombotic effect of homocysteine by demonstrating direct blockade of the tissue plasminogen activator binding domain of annexin II. Hajjar, K.A., Mauri, L. Jacovina, A.T. Zhong, F., Mirza U.A., Padovan, J.C., Chait, B.T. J. Biol. Chem. 1998, Apr 17 273(16) 9987-9993,
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Annexin 2 in Angiogenesis
  • 批准号:
    8098802
  • 项目类别:
  • 资助金额:
    $42.25万
  • 财政年份:
    2008
  • 负责人:
    KATHERINE AMBERSON HAJJAR
  • 依托单位:
Annexin 2 in Angiogenesis
  • 批准号:
    7665318
  • 项目类别:
  • 资助金额:
    $42.25万
  • 财政年份:
    2008
  • 负责人:
    KATHERINE AMBERSON HAJJAR
  • 依托单位:
IDENTIFICATION OF PUTATIVE PROTEIN CANDIDATES IN THE EXPORT MECHANISM OF ANNEXI
  • 批准号:
    7722216
  • 项目类别:
  • 资助金额:
    $0.11万
  • 财政年份:
    2008
  • 负责人:
    KATHERINE AMBERSON HAJJAR
  • 依托单位:
Annexin 2 in Angiogenesis
  • 批准号:
    7906827
  • 项目类别:
  • 资助金额:
    $42.25万
  • 财政年份:
    2008
  • 负责人:
    KATHERINE AMBERSON HAJJAR
  • 依托单位:
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