Reactome | prekallikrein:kininogen:C1q binding protein tetramer -> kallikrein:kininogen:C1q binding protein tetramer

prekallikrein:kininogen:C1q binding protein tetramer -> kallikrein:kininogen:C1q binding protein tetramer

Stable Identifier

R-HSA-158251

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

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prekallikrein:kininogen:C1q binding protein tetramer -> kallikrein:kininogen:C1q binding protein tetramer

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Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998).

Literature References

PubMed ID	Title	Journal	Year
8344943	Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C). Similarity to both serine carboxypeptidase and prolylendopeptidase families. Tan, F, Morris, PW, Skidgel, RA, Erdos, EG	J Biol Chem	1993
11830581	Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator Shariat-Madar, Z, Mahdi, F, Schmaier, AH	J Biol Chem	2002
28321	Purification and properties of prolylcarboxypeptidase (angiotensinase C) from human kidney Odya, CE, Marinkovic, DV, Hammon, KJ, Stewart, TA, Erdos, EG	J Biol Chem	1978
12123826	Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator Moreira, CR, Schmaier, AH, Mahdi, F, Motta, G, Nader, HB, Shariat-Madar, Z	FEBS Lett	2002
14996700	Recombinant prolylcarboxypeptidase activates plasma prekallikrein Shariat-Madar, Z, Mahdi, F, Schmaier, AH	Blood	2004