Reactome | kallikrein:kininogen:cell surface receptor -> kallikrein + cleaved kininogen:cell surface receptor + bradykinin

kallikrein:kininogen:cell surface receptor -> kallikrein + cleaved kininogen:cell surface receptor + bradykinin

Stable Identifier

R-HSA-9938539

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

kallikrein:kininogen:cell surface receptor -> kallikrein + cleaved kininogen:cell surface receptor + bradykinin

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The proteolytic cleavage of high molecular weight kininogen (HK), encoded by the KNG1 gene, converts a single-chain protein (depicted here as KNG1(19–644)) into a two-chain cleaved kininogen, releasing the vasoactive peptide bradykinin (KNG1(381-389)) (Kerbirou DM and Griffin JH 1979; Lottspeich F et al. 1985; Kellerman J et al. 1986). In vivo, this reaction is catalyzed by activated plasma kallikrein, takes places within the kallikrein:kininogen:cellsurface receptor complex, primarily on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta G et al. 1998; Zhao Y et al., 2001). Bradykinin binds to the B2 receptor (B2R), triggering inflammatory responses in a wide variety of cells. Cleaved kininogen has been implicated in the regulation of angiogenesis and cell adhesion (Asakura S et al., 1992; Asakura S et al., 1998; reviewed by Guo YL & Colman RW, 2005; Schmaier AH, 2016).

Literature References

PubMed ID	Title	Journal	Year
3484703	Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication. Kellermann, J, Lottspeich, F, Henschen, A, Muller-Esterl, W	Eur J Biochem	1986
500690	Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma. Kerbiriou, DM, Griffin, JH	J Biol Chem	1979
4054110	The amino acid sequence of the light chain of human high-molecular-mass kininogen Lottspeich, F, Kellermann, J, Henschen, A, Foertsch, B, Muller-Esterl, W	Eur J Biochem	1985
9427705	High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation Motta, G, Rojkjaer, R, Hasan, AA, Cines, DB, Schmaier, AH	Blood	1998