KALLIKREIN-KININ CASCADE PATHWAY (PW:0000526)

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Description

Kallikrein-kinin (KKS) cascade pathway leads to the production of active kinin peptides whose signaling via two G-protein coupled (GPCR) receptors prompts a range of responses that include vasodilation, release of inflammatory mediators, stimulation of sensory neurons. Recent studies also point to a potential role in oxidative stress. All active peptides are derived from a single precursor - kininogen (Kng1). Alternative splicing of Kng1 gives rise to the high- and low-molecular weight kinino

Pathway Diagram:

Elsevier Inc. Bdkrb2 F12a --+> coagulation cascade pathway F12a --+> classical complement pathway highKng1 ---> BK Bdkrb1 des-Arg-kinins ---> inflammatory mediators release kinin signaling pathway des-Arg-kinins ---> vasodilation BK ---> inflammatory mediators release KD ---> inflammatory mediators release inflammatory mediators release des-Arg-kinins ---> sensory neuron stimulation vasodilation des-Arg-kinins sensory neuron stimulation KD ---> vasodilation BK ---> vasodilation BK ---> sensory neuron stimulation KD ---> sensory neuron stimulation KD BK lowKng1 ---> KD BK ---> des-Arg-kinins Kng1 lowKng1 highKng1 kininases Serping1 Serpina4 Serpina4 ---| Klk1 A2m ---| Klkb1 Serping1 ---| Klkb1 Prcp --+> Klkb1 F12a --+> Klkb1 classical complement pathway coagulation cascade pathway Serping1 ---| F12a Klkb1 --+> F12a Klk1 KD ---> des-Arg-kinins Bdkrb2 ---- BK Bdkrb2 ---- KD Bdkrb1 ---- des-Arg-kinins des-Arg-kinins ---> inactive kinins inactive kinins Cpn1 Cpm pKlkb1 highKng1 ---- pKlkb1 F12 --+> F12a F12 A2m Kng1 ---> highKng1 Prcp Klkb1 F12a BK ---> inactive kinins KD ---> inactive kinins Kng1 ---> lowKng1
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Genes in Pathway:

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kallikrein-kinin cascade pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G A2m alpha-2-macroglobulin JBrowse link 4 154,309,426 154,359,138 RGD:7401223
G Ace angiotensin I converting enzyme JBrowse link 10 94,170,766 94,213,831 RGD:7401223
G Bdkrb1 bradykinin receptor B1 JBrowse link 6 129,437,423 129,441,553 RGD:7401223
G Bdkrb2 bradykinin receptor B2 JBrowse link 6 129,399,468 129,429,676 RGD:7401223
G Cpm carboxypeptidase M JBrowse link 7 60,654,350 60,714,620 RGD:7401223
G Cpn1 carboxypeptidase N subunit 1 JBrowse link 1 263,733,887 263,762,758 RGD:7401223
G F12 coagulation factor XII JBrowse link 17 9,736,577 9,744,420 RGD:7401223
G Klk1 kallikrein 1 JBrowse link 1 100,131,562 100,135,556 RGD:7401223
G Klkb1 kallikrein B1 JBrowse link 16 50,151,127 50,175,407 RGD:7401224
RGD:7401223
G Kng2 kininogen 2 JBrowse link 11 81,509,185 81,516,759 RGD:7401223
G Prcp prolylcarboxypeptidase JBrowse link 1 157,701,089 157,750,177 RGD:7401224
G Serpina4 serpin family A member 4 JBrowse link 6 127,743,883 127,753,047 RGD:7401223
G Serping1 serpin family G member 1 JBrowse link 3 72,161,230 72,171,109 RGD:7401223
G Xpnpep1 X-prolyl aminopeptidase 1 JBrowse link 1 273,708,217 273,758,247 RGD:7401223
G Xpnpep2 X-prolyl aminopeptidase 2 JBrowse link X 134,940,656 134,969,874 RGD:7401223
kinin signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Arrb1 arrestin, beta 1 JBrowse link 1 164,502,099 164,573,947 RGD:7411621
G Arrb2 arrestin, beta 2 JBrowse link 10 57,040,252 57,048,045 RGD:7411621
G Bdkrb1 bradykinin receptor B1 JBrowse link 6 129,437,423 129,441,553 RGD:7401223
RGD:7401225
G Bdkrb2 bradykinin receptor B2 JBrowse link 6 129,399,468 129,429,676 RGD:7401223
RGD:7401225
G Grk4 G protein-coupled receptor kinase 4 JBrowse link 14 81,261,708 81,339,516 RGD:7401225
G Kng2 kininogen 2 JBrowse link 11 81,509,185 81,516,759 RGD:7401223

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Functional Classkininasesthe kinin peptides metabolizing enzymes

Pathway Gene Annotations

Pathway Annotations Associated with Genes in the kallikrein-kinin cascade pathway
Pathway TermsGene Symbols
acenocoumarol pharmacodynamics pathwayF12 , Klkb1
alteplase pharmacodynamics pathwayF12 , Klkb1
Alzheimer disease pathwayA2m
aminocaproic acid pharmacodynamics pathwayF12 , Klkb1
angiotensin (1-7) signaling pathwayAce
angiotensin II signaling pathwayAce
anistreplase pharmacodynamics pathwayF12 , Klkb1
aprotinin pharmacodynamics pathwayF12 , Klkb1
argatroban pharmacodynamics pathwayF12 , Klkb1
benazepril pharmacodynamics pathwayAce
benazepril pharmacokinetics pathwayAce
bivalirudin pharmacodynamics pathwayF12 , Klkb1
calcium/calcium-mediated signaling pathwayBdkrb1 , Bdkrb2
candesartan pharmacodynamics pathwayAce
captopril pharmacodynamics pathwayAce
cilazapril pharmacodynamics pathwayAce
cilazapril pharmacokinetics pathwayAce
coagulation cascade pathwayA2m , Bdkrb1 , Bdkrb2 , F12 , Klkb1 , Kng2 , Serping1
complement system pathwayA2m , Bdkrb1 , Bdkrb2 , F12 , Klkb1 , Kng2 , Serping1
dicoumarol pharmacodynamics pathwayF12 , Klkb1
enalapril pharmacodynamics pathwayAce
enalapril pharmacokinetics pathwayAce
enoxaparin pharmacodynamics pathwayF12 , Klkb1
eprosartan pharmacodynamics pathwayAce
fondaparinux pharmacodynamics pathwayF12 , Klkb1
forasartsn pharmacodynamics pathwayAce
fosinopril pharmacodynamics pathwayAce
fosinopril pharmacokinetics pathwayAce
G protein mediated signaling pathway via Galphai familyBdkrb1 , Bdkrb2
G protein mediated signaling pathway via Galphaq familyBdkrb1 , Bdkrb2
heparin pharmacodynamics pathwayF12 , Klkb1
hypertrophic cardiomyopathy pathwayAce
immune response pathwayA2m
inflammatory response pathwayA2m
interleukin-6 signaling pathwayA2m
irbesartan pharmacodynamics pathwayAce
kallikrein-kinin cascade pathwayA2m , Ace , Bdkrb1 , Bdkrb2 , Cpm , Cpn1 , F12 , Klk1 , Klkb1 , Kng2 , Prcp , Serpina4 , Serping1 , Xpnpep1 , Xpnpep2
kinin signaling pathwayBdkrb1 , Bdkrb2 , Kng2
lisinopril pharmacodynamics pathwayAce
losartan pharmacodynamics pathwayAce
moexipril pharmacodynamics pathwayAce
moexipril pharmacokinetics pathwayAce
olmesartan pharmacodynamics pathwayAce
perindopril pharmacodynamics pathwayAce
phenindione pharmacodynamics pathwayF12 , Klkb1
quinapril pharmacodynamics pathwayAce
quinapril pharmacokinetics pathwayAce
ramipril pharmacodynamics pathwayAce
ramipril pharmacokinetics pathwayAce
renin-angiotensin cascade pathwayAce
reteplase pharmacodynamics pathwayF12 , Klkb1
spirapril pharmacodynamics pathwayAce
spirapril pharmacokinetics pathwayAce
syndecan signaling pathwayKng2
telmisartan pharmacodynamics pathwayAce
trandolapril pharmacodynamics pathwayAce
trandolapril pharmacokinetics pathwayAce
tranexamic acid pharmacodynamics pathwayF12 , Klkb1
transforming growth factor-beta Smad dependent signaling pathwayA2m
Trypanosoma cruzi infection pathwayAce , Bdkrb2
valsartan pharmacodynamics pathwayAce
warfarin pharmacodynamics pathwayF12 , Klkb1
Phenotype Annotations Associated with Genes in the kallikrein-kinin cascade pathway

References Associated with the kallikrein-kinin cascade pathway:

Ontology Path Diagram:

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