Identification of prolylcarboxypeptidase as the cell matrix‐associated prekallikrein activator

FEBS Letters

Moreira, Claudia R²  Schmaier, Alvin H¹  Mahdi, Fakhri¹  Shariat-Madar, Zia¹  da Motta, Guacyara²  Nader, Helena B² 

[1] Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA;Departmento de Bioquimica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

关键词: Prolylcarboxypeptidase;    Lysosomal carboxypeptidase;    Angiotensinase C;    Prekallikrein;    Single chain urokinase;    Angiotensin II;    Bradykinin;    HK;    high molecular weight kininogen;    PK;    prekallikrein;    HUVEC;    human umbilical vein endothelial cells;    CTI;    corn trypsin inhibitor;    PRCP;    prolylcarboxypeptidase;    ATII;    angiotensin II;    BK;    bradykinin;    Ang 1–7;    angiotensin 1–7;    BK 1–5;    bradykinin 1–5;    ZPP-OH;    Z-Pro-Pro-OH;    FMOC;    Fmoc-aminoacylpyrrolidine-2-nitrile;    ScuPA;    single chain urokinase plasminogen activator;   

DOI  :  10.1016/S0014-5793(02)02980-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Investigations determined that the cell matrix-associated prekallikrein (PK) activator is prolylcarboxypeptidase. PK activation on human umbilical vein endothelial cell (HUVEC) matrix is inhibited by antipain (IC₅₀=50 μM) but not anti-factor XIIa antibody, 3 mM benzamidine, 5 mM iodoacetic acid or iodoacetamide, or 3 mM N-ethylmaleimide. Corn trypsin inhibitor (IC₅₀=100 nM) or Fmoc-aminoacylpyrrolidine-2-nitrile (IC₅₀=100 μM) blocks matrix-associated PK activation. Angiotensin II (IC₅₀=100 μM) or bradykinin (IC₅₀=3 mM), but not angiotensin 1–7 or bradykinin 1–5, inhibits matrix-associated PK activation. ECV304 cell matrix PK activator also is blocked by 100 μM angiotensin II, 1 μM corn trypsin inhibitor, and 50 μM antipain, but not angiotensin 1–7. 1 mM angiotensin II or 300 μM Fmoc-aminoacylpyrrolidine-2-nitrile indirectly blocks plasminogen activation by inhibiting kallikrein formation for single chain urokinase activation. On immunoblot, prolylcarboxypeptidase antigen is associated with HUVEC matrix. These studies indicate that prolylcarboxypeptidase is the matrix PK activator.

【 授权许可】

Unknown