Download PDF
Thromb Haemost 2000; 84(04): 657-663
DOI: 10.1055/s-0037-1614083
Review Article
Schattauer GmbH

Tissue Factor Encryption/de-encryption Is not Altered in the Absence of the Cytoplasmic Domain

Steven D. Carson
1   From the Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE
,
Michael E. Bromberg
2   Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
› Author AffiliationsThis research was partially supported by grant K11-CA64205 from the National Cancer Institute and a Junior Faculty Scholar Award from the American Society of Hematology (M.E.B.), and by funds from the University of Nebraska Medical Center seed grant program (S.D.C.). Technical assistance was provided by Mr. Justin Hobbs.
Further Information

Publication History

Received 03 January 2000

Accepted after revision 14 April 2000

Publication Date:
11 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Since the cytoplasmic domain of tissue factor (TF) appears to have a role in TF function beyond coagulation, experiments were conducted to determine whether the cytoplasmic domain also has a role in regulating procoagulant activity of TF present in the cell membrane. TF encryption was quantitated in human YU-SIT1, U87-MG, and mouse 3T3 cells which were transfected for expression of human tissue factor or a construct lacking the cytoplasmic domain (TFCD). Comparison of intact cells (encrypted) with fully disrupted cells (de-encrypted) showed that TF and TFCD were equally encrypted with respect to function in fX activation. Moreover, cells expressing TF and TFCD were indistinguishable in their procoagulant responses to A23187-calcium and varied concentrations of nonionic detergents. TF in membrane vesicles spontaneously shed by U87-MG cells was largely, but incompletely, de-encrypted, and the degree of de-encryption was independent of the cytoplasmic domain. We conclude that the predominant mechanism(s) for encrypting TF procoagulant activity is independent of the cytoplasmic domain.

Key words

Tissue factor - encryption - cytoplasmic domain
 

  • References

  • 1 Maynard JR, Heckman CA, Pitlick FA, Nemerson Y. Association of tissue factor activity with the surface of cultured cells. J Clin Invent 1975; 55: 814-24.
    PubMedGoogle Scholar
  • 2 Carson SD, Archer PG. Tissue factor in HeLa cells measured with a continuous chromogenic assay and ELISA reader. Thrombos Res 1986; 41: 185-95.
    CrossrefPubMedGoogle Scholar
  • 3 Carson SD, Pirruccello SJ, Haire WD. Tissue factor antigen and activity are not expressed on the surface of intact cells isolated from an acute promyelocytic leukemia patient. Thromb Res 1990; 59: 159-70.
    CrossrefPubMedGoogle Scholar
  • 4 Camera M, Giesen PLA, Fallon J, Aufiero BM, Taubman M, Tremoli E, Nemerson Y. Cooperation between VEGF and TNF-a is necessary for exposure of active tissue factor on the surface of human endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 531-7.
    CrossrefPubMedGoogle Scholar
  • 5 Broze Jr GJ. Binding of human factor VII and VIIa to monocytes. J Clin Invest 1982; 70: 526-35.
    CrossrefPubMedGoogle Scholar
  • 6 Drake TA, Ruf W, Morrissey JH, Edgington TS. Functional tissue factor is entirely cell surface expressed on lipopolysaccharide-stimulated human blood monocytes and a constitutively tissue factor-producing neoplastic cell line. J Cell Biol 1989; 109: 389-95.
    CrossrefPubMedGoogle Scholar
  • 7 Le DT, Rapaport SI, Rao LVM. Relations between factor VIIa binding and expression of factor VIIa/tissue factor catalytic activity on cell surfaces. J Biol Chem 1992; 267: 15447-54.
    PubMedGoogle Scholar
  • 8 Mann KG. The assembly of blood clotting complexes on membranes. TIBS 1987; 12: 229-33.
    PubMedGoogle Scholar
  • 9 Cutsforth GA, Whitaker RN, Hermans J, Lentz BR. A new model to describe extrinsic protein binding to phospholipid membranes of varying composition: application to human coagulation proteins. Biochemistry 1989; 28: 7453-61.
    CrossrefPubMedGoogle Scholar
  • 10 Bach R, Gentry R, Nemerson Y. Factor VII binding to tissue factor in reconstituted phospholipid vesicles: induction of cooperativity by phosphatidylserine. 1986; 25: 4007-20.
    PubMedGoogle Scholar
  • 11 Bach R, Rifkin DB. Expression of tissue factor procoagulant activity: regulation by cytosolic calcium. Proc Natl Acad Sci 1990; 87: 6995-9.
    CrossrefPubMedGoogle Scholar
  • 12 Carson SD. Manifestation of cryptic fibroblast tissue factor occurs at detergent concentrations which dissolve the plasma membrane. Blood Coagulation and Fibrinolysis 1996; 07: 303-13.
    CrossrefPubMedGoogle Scholar
  • 13 Le DT, Rapaport SI, Rao LVM. Studies of the mechanism for enhanced cell surface factor VIIa/tissue factor activation of factor X on fibroblast monolayers after their exposure to N-ethylmaleimide. Thromb Haemost 1994; 72: 848-55.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Carson SD, Kuszynski CA, Pirruccello SJ. Fibroblasts restrict tissue factor from vesicles which form in response to low concentrations of detergent. Blood Coagulation and Fibrinolysis 1996; 07: 314-24.
    CrossrefPubMedGoogle Scholar
  • 15 Bouchard BA, Shatos MA, Tracy PB. Human brain pericytes differentially regulate expression of procoagulant enzyme complexes comprising the extrinsic pathway of blood coagulation. Arterioscler Thromb Vasc Biol 1997; 17: 1-9.
    CrossrefPubMedGoogle Scholar
  • 16 Wolberg AS, Monroe DM, Roberts HR, Hoffman MR. Tissue factor deencryption: ionophore treatment induces changes in tissue factor activity by phosphatidylserine-dependent and -independent mechanisms. Blood Coag Fibrinol 1999; 10: 201-10.
    CrossrefPubMedGoogle Scholar
  • 17 Bach RR, Moldow CF. Mechanism of tissue factor activation on HL-60 cells. Blood 1997; 89: 3270-6.
    PubMedGoogle Scholar
  • 18 Mulder AB, Smit JW, Bom VJJ, Blom NR, Ruiters MHJ, Halie MR, van der Meer J. Association of smooth muscle cell tissue factor with caveolae. 1996; 88: 1306-13.
    PubMedGoogle Scholar
  • 19 Sevinsky JR, Rao LVM, Ruf W. Ligand-induced protease receptor translocation into caveolae: A mechanism for regulating cell surface proteolysis of the tissue factor-dependent coagulation pathway. J Cell Biol 1996; 133: 293-304.
    CrossrefPubMedGoogle Scholar
  • 20 Hansen CB, van Deurs B, Petersen LC, Rao LVM. Discordant expression of tissue factor and its activity in polarized epithelial cells. Asymmetry in anionic phospholipid availability as a possible explanation. Blood 1999; 94: 1657-64.
    PubMedGoogle Scholar
  • 21 Bouchard BA, Shatos MA, Tracy PB. Human brain pericytes differentially regulate expression of procoagulant enzyme complexes comprising the extrinsic pathway of blood coagulation. Arterioscler Thromb Vasc Biol 1997; 17: 1-9.
    CrossrefPubMedGoogle Scholar
  • 22 Muller M, Albrecht S, Golfert F, Hofer A, Funk RHW, Magdolen V, Flossel C, Luther T. Localization of tissue factor in actin-filament-rich membrane areas of epithelial cells. Expt Cell Res 1999; 248: 136-47.
    CrossrefPubMedGoogle Scholar
  • 23 Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140: 1241-53.
    CrossrefPubMedGoogle Scholar
  • 24 Zioncheck TF, Roy S, Vehar GA. The cytoplasmic domain of tissue factor is phosphorylated by a protein kinase C-dependent mechanism. J Biol Chem 1992; 267: 3561-4.
    PubMedGoogle Scholar
  • 25 Mody RS, Carson SD. Tissue factor cytoplasmic domain peptide is multiply phosphorylated in vitro. 1997; 36: 7869-75.
    PubMedGoogle Scholar
  • 26 Rottingen J-A, Enden T, Camerer E, Iversen J-G, Prydz H. Binding of human factor VIIa to tissue factor induces cytosolic Ca+2 signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor. J Biol Chem 1995; 270: 4650-60.
    CrossrefPubMedGoogle Scholar
  • 27 Poulsen LK, Jacobsen N, Sorensen BB, Bergenhem NCH, Kelly JD, Foster DC, Thastrup O, Ezban M, Petersen LC. Signal transduction via the mitogen-activated protein kinase pathway induced by binding of coagulation factor VIIa to tissue factor. J Biol Chem 1998; 273: 6228-32.
    CrossrefPubMedGoogle Scholar
  • 28 Cunningham MA, Romas P, Hutchinson P, Holdsworth Sr, Tipping PG. Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages. Blood 1999; 94: 3413-20.
    PubMedGoogle Scholar
  • 29 Bromberg ME, Konigsberg WH, Madison J, Pawashe A, Garen A. Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proc Natl Acad Sci USA 1995; 92: 8205-9.
    CrossrefPubMedGoogle Scholar
  • 30 Bromberg ME, Sundaram R, Homer RJ, Garen A, Konigsberg WH. Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost 1999; 82: 88-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Mueller B, Ruf W. Requirement fo binding of catalytically active factor VIIa in tissue factor-dependent experimental metastasis. J Clin Invest 1998; 101: 1372-8.
    CrossrefPubMedGoogle Scholar
  • 32 Abe K, Shoji M, Bierhaus A, Danave I, Micko C, Casper K, Dillehay Dl, Nawroth PP, Rickles FR. Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci USA 1999; 96: 8663-8.
    CrossrefPubMedGoogle Scholar
  • 33 Sorensen BB, Freskgard PO, Nielson LS, Rao LV, Ezban M, Petersen LC. Factor VIIa-induced p44/42 mitogen-activated protein kinase activation requires the proteolytic activity of factor VIIa and is independent of the tissue factor cytoplasmic domain. J Biol Chem 1999; 274: 21349-54.
    CrossrefPubMedGoogle Scholar
  • 34 Paborsky LR, Caras IW, Fisher KL, Gorman CM. Lipid association, but not the transmembrane domain, is required for tissue factor activity. J Biol Chem 1991; 266: 21911-6.
    PubMedGoogle Scholar
  • 35 Towbin H, Theophil S, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-4.
    CrossrefPubMedGoogle Scholar
  • 36 Carson SD, Ross SE, Bach R, Guha A. An inhibitory monoclonal antibody against human tissue factor. Blood 1987; 70: 490-3.
    PubMedGoogle Scholar
  • 37 Carson SD, Yoder SC. Monoclonal antibodies against the C-terminal peptide of human tissue factor for studies of the cytoplasmic domain. Blood Coagulation and Fibrinolysis 1992; 03: 779-87.
    CrossrefPubMedGoogle Scholar
  • 38 Carson SD, Pirruccello SJ. Immunofluorescent studies of tissue factor on U87MG cells: evidence for non-uniform distribution. Blood Coag Fibrinol 1993; 04: 911-20.
    CrossrefPubMedGoogle Scholar
  • 39 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5.
    CrossrefPubMedGoogle Scholar
  • 40 Carson SD. Computerized analysis of enzyme cascade reactions using continuous rate data obtained with an ELISA reader. Computer Progr Biomed 1985; 19: 151-7.
    CrossrefPubMedGoogle Scholar
  • 41 Carson SD. Manifestation of cryptic fibroblast tissue factor occurs at detergent concentrations which dissolve the plasma membrane. 1996; 07: 303-93.
    PubMedGoogle Scholar
  • 42 Edwards AL. Multiple Regression and the Analysis of Variance and Covariance. 2nd ed. New York: W. H. Freeman and Company; 1985
    Google Scholar
  • 43 Miletich JP, Broze GJJ, Majerus PW. Purification of human coagulation factors II, IX, and X using sulfated dextran beads. Methods Enzymol 1981; 80: 221-8.
    PubMedGoogle Scholar
  • 44 Bastida E, Ordinas A, Escolar G, Janieson GA. Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation, and thrombogenesis. Blood 1984; 64: 177-84.
    PubMedGoogle Scholar
  • 45 Carson SD, Perry GA, Pirruccello SJ. Fibroblast tissue factor: calcium and ionophore induce shape changes, release of membrane vesicles, and redistribution of tissue factor antigen in addition to increased procoagulant activity. Blood 1994; 84: 526-34.
    PubMedGoogle Scholar
  • 46 Camerer E, Pringle S, Skartlien AH, Wiiger M, Prydz K, Kolsto A-B, Prydz H. Opposite sorting of tissue factor in human unbilical vein endothelial cells and Madin-Darby canine kidney epithelial cells. Blood 1996; 88: 1339-49.
    PubMedGoogle Scholar