Molecules in focus - Thrombin

被引:101
作者
Goldsack, NR [1 ]
Chambers, RC [1 ]
Dabbagh, K [1 ]
Laurent, GJ [1 ]
机构
[1] UCL, Rayne Inst, Ctr Cardiopulm Biochem & Resp Res, London WC1E 6BT, England
关键词
thrombin; serine protease; receptors; therapies;
D O I
10.1016/S1357-2725(98)00011-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thrombin is a multifunctional serine protease which plays a central role in haemostasis by regulating platelet aggregation and blood coagulation. It is formed from its precursor prothrombin following tissue injury and converts fibrinogen to fibrin in the final step of the clotting cascade. It also promotes numerous cellular effects including chemotaxis, proliferation. extracellular matrix turnover and release of cytokines. These actions of thrombin on cells have been implicated in tissue repair processes and in the pathogenesis of inflammatory and fibroproliferative disorders such as pulmonary fibrosis and atherosclerosis. Thrombin mediates its cellular effects by proteolytically activating cell surface receptors. Presently, two such receptors have been described and their roles in regulation of these functions are currently being investigated. The discovery of multiple thrombin receptors creates the possibility of selective receptor blockade of specific thrombin mediated events. New drugs with these actions should add to our current repertoire of thrombin inhibitors used to treat thrombotic diseases. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:641 / 646
页数:6
相关论文
共 18 条
  • [1] DECREASES IN PROTEASE NEXINS IN ALZHEIMERS-DISEASE BRAIN
    CHOI, BH
    KIM, RC
    VAUGHAN, PJ
    LAU, A
    VANNOSTRAND, WE
    COTMAN, CW
    CUNNINGHAM, DD
    [J]. NEUROBIOLOGY OF AGING, 1995, 16 (04) : 557 - 562
  • [2] Role of the thrombin receptor In development and evidence for a second receptor
    Connolly, AJ
    Ishihara, H
    Kahn, ML
    Farese, RV
    Coughlin, SR
    [J]. NATURE, 1996, 381 (6582) : 516 - 519
  • [3] AN ANTIBODY AGAINST THE EXOSITE OF THE CLONED THROMBIN RECEPTOR INHIBITS EXPERIMENTAL ARTERIAL THROMBOSIS IN THE AFRICAN-GREEN MONKEY
    COOK, JJ
    SITKO, GR
    BEDNAR, B
    CONDRA, C
    MELLOTT, MJ
    FENG, DM
    NUTT, RF
    SHAFER, JA
    GOULD, RJ
    CONNOLLY, TM
    [J]. CIRCULATION, 1995, 91 (12) : 2961 - 2971
  • [4] Darrow AL, 1996, THROMB HAEMOSTASIS, V76, P860
  • [5] CHARACTERIZATION OF THE COMPLEMENTARY DEOXYRIBONUCLEIC-ACID AND GENE CODING FOR HUMAN-PROTHROMBIN
    DEGEN, SJF
    MACGILLIVRAY, RTA
    DAVIE, EW
    [J]. BIOCHEMISTRY, 1983, 22 (09) : 2087 - 2097
  • [6] Cellular consequences of thrombin-receptor activation
    Grand, RJA
    Turnell, AS
    Grabham, PW
    [J]. BIOCHEMICAL JOURNAL, 1996, 313 : 353 - 368
  • [7] Herbert JM, 1997, J CELL PHYSIOL, V170, P106, DOI 10.1002/(SICI)1097-4652(199702)170:2<106::AID-JCP2>3.0.CO
  • [8] 2-S
  • [9] ROLE OF THROMBIN IN PULMONARY FIBROSIS
    HERNANDEZRODRIGUEZ, NA
    CAMBREY, AD
    HARRISON, NK
    CHAMBERS, RC
    GRAY, AJ
    SOUTHCOTT, AM
    DUBOIS, RM
    BLACK, CM
    SCULLY, MF
    MCANULTY, RJ
    LAURENT, GJ
    [J]. LANCET, 1995, 346 (8982): : 1071 - 1073
  • [10] Hewett PW, 1996, INT J CANCER, V66, P784, DOI 10.1002/(SICI)1097-0215(19960611)66:6<784::AID-IJC13>3.3.CO