Reactome | kallikrein:kininogen:cell surface receptor:factor XII -> kallikrein:kininogen:cell surface receptor + factor XIIa (kallikrein catalyst)

kallikrein:kininogen:cell surface receptor:factor XII -> kallikrein:kininogen:cell surface receptor + factor XIIa (kallikrein catalyst)

Stable Identifier

R-HSA-9909046

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

Synonyms

kallikrein:KNG1:(C1QBP,C1QBP:KRT1, PLAUR:KRT1):FXII -> FXIIa + kallikrein:KNG1:(C1QBP, C1QBP:KRT1, PLAUR:KRT1)

ReviewStatus

5/5

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kallikrein:kininogen:cell surface receptor:factor XII -> kallikrein:kininogen:cell surface receptor + factor XIIa (kallikrein catalyst)

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Binding of factor XII (FXII) to cell surface receptors facilitates the assembly of high molecular weight kininogen (HK), prekallikrein (PK), and FXII into higher order ternary complexes, in which FXIIa and plasma kallikrein (PKa) mutually activate each other in a Zn²⁺-dependent manner, creating a positive feedback loop on the cell surface (Joseph K et al., 1999, 2001, 2004; Mahdi F et al., 2002, 2003; Kaira BG et al., 2020; reviewed by Pathak M et al., 2018). This Reactome event describes plasma kallikrein-catalyzed cleavage of FXII within the cell surface receptor complexes, leading to the release of activated FXIIa. The cell surface receptors involved in this process include complement C1q binding protein, encoded by the C1QBP gene, also known as globular C1q receptor (gC1qR), cytokeratin 1 (CK1, encoded by the KRT1 gene), and the urokinase plasminogen activator receptor (uPAR, encoded by the PLAUR gene). Both gC1qR (C1QBP) and uPAR (PLAUR) interact with CK1, forming heterodimers gC1qR:CK1 and uPAR:CK1 complexes, respectively. Additionally, gC1qR (C1QBP) may function as a homotrimer (Ghebrehiwet B et al., 1994; Joseph K et al., 1999, 2001, 2004; Mahdi F et al., 2002, 2003; Kaira BG et al., 2020; reviewed by Pathak M et al., 2018). Although gC1qR, CK1 and uPAR are expressed on various cell types, including activated platelets (Peerschke EIB et al., 2003; Khan MM et al., 2006; reviewed by Schmaier AH, 2016), FXII induced activation of the plasma kallikrein kinin system is thought to occur predominantly on endothelial cell surfaces (Lin Y et al., 1997; Motta G et al., 1998; Joseph K et al., 2001; Mahdi F et al., 2002, 2003; Pixley RA et al., 2011; Kaira BG et al., 2020).

Literature References

PubMed ID	Title	Journal	Year
11204562	Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1 Joseph, K, Shibayama, Y, Ghebrehiwet, B, Kaplan, AP	Thromb Haemost	2001
25039405	Single-chain factor XII exhibits activity when complexed to polyphosphate Engel, R, Brain, CM, Paget, J, Lionikiene, AS, Mutch, NJ	J Thromb Haemost	2014
14691562	The physiologic basis of assembly and activation of the plasma kallikrein/kinin system Schmaier, AH	Thromb Haemost	2004
874082	Activation and function of human Hageman factor. The role of high molecular weight kininogen and prekallikrein. Meier, HL, Pierce, JV, Colman, RW, Kaplan, AP	J Clin Invest	1977
32559765	Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery Kaira, BG, Slater, A, McCrae, KR, Dreveny, I, Sumya, U, Mutch, NJ, Searle, M, Emsley, J	Blood	2020
11986212	Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes Mahdi, F, Shariat-Madar, Z, Figueroa, CD, Schmaier, AH	Blood	2002