An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface Journal Article


Authors: Deora, A. B.; Kreitzer, G.; Jacovina, A. T.; Hajjar, K. A.
Article Title: An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface
Abstract: 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, overexpression of annexin 2 in acute promyelocytic leukemia leads to a bleeding diathesis reflective of excessive cell surface annexin 2-dependent generation of plasmin (Menell, J. S., Cesarman, G. M., Jacovina, A. T., McLaughlin, M. A., Lev, E. A., and Hajjar, K. A. (1999) N. Engl. J. Med. 340, 994-1004). In addition, mice completely deficient in annexin 2 display fibrin accumulation within blood vessels and impaired clearance of injury-induced thrombi (Ling Q., Jacovina, A.T., Deora, A.B., Febbraio, M., Simantov, R., Silverstein, R. L., Hempstead, B. L., Mark, W., and Hajjar, K. A. (2004) J. Clin. Investig. 113, 38-48). Here, we show 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 reticulum-Golgi pathway. Temperature stress-induced annexin 2 translocation is dependent on both expression of protein p11 (S100A10) and tyrosine phosphorylation of annexin 2 because annexin 2 release 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.
Keywords: signal transduction; controlled study; protein expression; protein phosphorylation; unclassified drug; human cell; mutation; cytology; cell death; cells, cultured; apoptosis; protein depletion; cell protein; intracellular transport; protein tyrosine kinase; tyrosine; phosphorylation; endothelium cell; cloning, molecular; endoplasmic reticulum; kinetics; endothelium, vascular; umbilical veins; messenger rna; protein synthesis; rna synthesis; enzyme inactivation; recombinant proteins; cell membrane; protein transport; protein secretion; cytoplasm; cytolysis; temperature; thermodynamics; lipocortin 2; blood vessels; tissue; dna, complementary; s100 proteins; golgi complex; cell surface; polypeptides; annexin a2; stimulus response; annexin; humans; human; priority journal; article; interfaces (materials); thermal stress; plasminogens; protein secretion pathways; protein p11; heat stress; molva molva
Journal Title: Journal of Biological Chemistry
Volume: 279
Issue: 42
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2004-10-15
Start Page: 43411
End Page: 43418
Language: English
DOI: 10.1074/jbc.M408078200
PROVIDER: scopus
PUBMED: 15302870
DOI/URL:
Notes: J. Biol. Chem. -- Cited By (since 1996):104 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Source: Scopus
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