IDENTIFICATION OF PUTATIVE PROTEIN CANDIDATES IN THE EXPORT MECHANISM OF ANNEXI

附件出口机制中推定候选蛋白质的鉴定

• 批准号: 7722216
• 负责人: KATHERINE AMBERSON HAJJAR
• 金额: $ 0.11万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722216
• 关键词: Acute Promyelocytic Leukemia; Alteplase; Annexins; Biological Assay; Blood Vessels; Cell Death; Cell membrane; Cell surface; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytolysis; Cytoplasm; Disease susceptibility; Endothelial Cells; Fibrin; Funding; Generations; Grant; Hemorrhage; In Vitro; Injury; Institution; Mass Spectrum Analysis; Messenger RNA; Mus; Mutation; Pathway interactions; Peptide Signal Sequences; Plasmin; Plasminogen; Protein Secretion; Protein Tyrosine Kinase; Proteins; Research; Research Personnel; Resources; S100 family protein p11; Source; Stress; Stress-Induced Protein; Temperature; Thrombus; Tyrosine; Tyrosine Phosphorylation; United States National Institutes of Health; human subject; in vivo; novel; plasminogen receptor; protein expression; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Annexin 2 is a profibrinolytic co-receptor for plasminogen and tissue plasminogen activator that stimulates activation of the major fibrinolysin, plasmin, at cell surfaces. In human subjects, over-expression of annexin 2 in acute promyelocytic leukemia leads to a bleeding diathesis reflective of excessive cell surface annexin 2-dependent generation of plasmin. In addition, mice completely deficient in annexin 2 display fibrin accumulation within blood vessels and impaired clearance of injury-induced thrombi. We have previously shown that endothelial cell annexin 2, a protein that lacks a typical signal peptide, translocates from the cytoplasm to the extracytoplasmic plasma membrane in response to brief temperature stress both in vitro and in vivo in the absence of cell death or cell lysis. This regulated response is independent of new protein or mRNA synthesis and does not require the classical endoplasmic reticulumGolgi pathway. Translocation of annexin 2 induced by temperature stress is dependent on both expression of protein p11 (S100A10) and tyrosine phosphorylation of annexin 2 because the release of annexin 2 is completely eliminated on depletion of p11, inactivation of tyrosine kinase, or mutation of tyrosine 23. Translocation of annexin 2 to the cell surface dramatically increases tissue plasminogen activator-dependent plasminogen activation potential and may represent a novel stress-induced protein secretion pathway. We have identified by immunoaffinity assays and mass spectrometry at least four proteins that may be associated with the translocation mechanism of annexin 2 to the cell surface. These putative protein candidates are currently being investigated.

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