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The kallikrein-kinin (KKS) cascade pathway generates the active kinin peptides. Kinin signaling plays important roles in the cardiovascular, renal, respiratory and nervous systems. It elicits vasodilator, inflammatory and pain responses and it exert both proliferating and anti-proliferating effects. The active kinin peptides bradykinin (BK), kallidin (KD) and their C-terminal processed des-Arg-metabolites signal via two G-protein coupled (GPCR) receptors, known as B1R and B2R, encoded by Bdkrb1

Pathway Diagram:

Elsevier Inc. des-Arg-kinins ---> vasodilation vasodilation des-Arg-kinins des-Arg-kinins ---> heart function Ca2+ --+> NO Ca2+ --+> arachidonic acid protein kinase C (PKC) signaling pathway --+> the extracellular signal-regulated Raf/Mek/Erk signaling pathway G protein mediated signaling pathway via Galphaq family --+> DAG G protein mediated signaling pathway via Galphaq family --+> IP3 IP3 Ca2+ calcium/calcium-mediated signaling pathway G protein mediated signaling pathway via Galphaq family G protein mediated signaling pathway via Galphai family BK Arrb2 ---- Bdkrb2 GRK4 ---> Bdkrb2 GRK4 heart function perception of pain BK ---> kidney function IP3 --+> Ca2+ DAG --+> protein kinase C (PKC) signaling pathway Arrb1 ---- Bdkrb2 Arrb1 Arrb2 Bdkrb2 ---- KD Bdkrb1 ---- des-Arg-kinins Bdkrb2 ---- BK kidney function Bdkrb1 Bdkrb2 KD ---> perception of pain Ca2+ --+> protein kinase C (PKC) signaling pathway KD DAG arachidonic acid NO calcium transport pathway protein kinase C (PKC) signaling pathway the extracellular signal-regulated Raf/Mek/Erk signaling pathway kallikrein-kinin cascade pathway G protein independent events

Genes in Pathway:

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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
G Bdkrb2 bradykinin receptor B2 JBrowse link 6 129,399,468 129,429,676 RGD:7401223
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
ProteinBKbradykinin generated via the kallikrein-kinin pathway
ProteinKDkallidin generated via the kallikrein-kinin pathway
Proteindes-Arg-kininthe kinins further derived from BK and KD in the kallikrein-kinin pathway

Pathway Gene Annotations

Disease Annotations Associated with Genes in the kinin signaling pathway
Disease TermsGene Symbols
3MC syndrome 1Kng2
Acquired AngioedemaKng2
acute kidney failureBdkrb2 , Kng2
acute myeloid leukemiaBdkrb1 , Bdkrb2
allergic hypersensitivity diseaseKng2
amphetamine abuseArrb2
Animal Disease ModelsBdkrb2 , Kng2
Animal Mammary NeoplasmsKng2
Arteriovenous FistulaArrb1 , Arrb2
Cardiac ArrhythmiasKng2
Chemical and Drug Induced Liver InjuryBdkrb2 , Grk4 , Kng2
chronic obstructive pulmonary diseaseBdkrb2
congestive heart failureArrb1
CoughBdkrb2 , Kng2
Diabetes ComplicationsBdkrb1 , Bdkrb2
Diabetes Mellitus, Experimental Bdkrb1 , Bdkrb2
diabetic angiopathyBdkrb1
Diabetic NephropathiesBdkrb2 , Grk4 , Kng2
diabetic neuropathyBdkrb1
diabetic retinopathyBdkrb1 , Bdkrb2
Drug EruptionsKng2
EdemaBdkrb1 , Kng2
end stage renal failureBdkrb1
EosinophiliaBdkrb2 , Kng2
epilepsyBdkrb1 , Bdkrb2
essential hypertensionGrk4
essential thrombocythemiaBdkrb1 , Bdkrb2
Experimental ArthritisArrb1 , Arrb2 , Bdkrb1 , Kng2
Experimental Liver CirrhosisArrb2 , Kng2
Experimental Liver NeoplasmsArrb2
Extravasation of Diagnostic and Therapeutic MaterialsBdkrb2 , Kng2
Flaujeac Factor DeficiencyKng2
focal segmental glomerulosclerosisBdkrb1
Henoch-Schoenlein purpuraKng2
hereditary angioedemaKng2
HyperalgesiaBdkrb1 , Bdkrb2 , Kng2
HyperemiaBdkrb2 , Kng2
hypertensionArrb2 , Bdkrb1 , Bdkrb2 , Kng2
HypotensionBdkrb2 , Kng2
InflammationBdkrb1 , Bdkrb2
Insulin ResistanceBdkrb1
Kidney Reperfusion InjuryBdkrb1
Left Ventricular HypertrophyBdkrb1 , Bdkrb2
liver cirrhosisArrb1
lung diseaseBdkrb2
major depressive disorderArrb1
malignant gliomaBdkrb2
Microvascular AnginaBdkrb1 , Bdkrb2
myelofibrosisBdkrb1 , Bdkrb2
myocardial infarctionBdkrb1 , Bdkrb2
Myocardial Reperfusion InjuryArrb2 , Kng2
occupational dermatitisBdkrb2 , Kng2
Overactive Urinary BladderBdkrb1
PainBdkrb1 , Bdkrb2 , Kng2
pleurisyBdkrb1 , Bdkrb2
portal hypertensionArrb2 , Bdkrb2
proliferative vitreoretinopathyKng2
pulmonary fibrosisBdkrb1
pulmonary hypertensionBdkrb2
renal fibrosisArrb2 , Bdkrb1
rheumatoid arthritisBdkrb2
rhinitisBdkrb1 , Bdkrb2
sciatic neuropathyBdkrb1 , Bdkrb2
Sudden Death, CardiacKng2
temporal lobe epilepsyBdkrb1 , Bdkrb2
Transplant RejectionArrb1 , Arrb2
type 2 diabetes mellitusArrb2
Vascular System InjuriesBdkrb1 , Bdkrb2
Venous ThromboembolismKng2
Pathway Annotations Associated with Genes in the kinin signaling pathway

References Associated with the kinin signaling pathway:

Ontology Path Diagram:

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