Thrombin-activated PARs activate G12/13

Stable Identifier
R-HSA-114552
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
G12/13 activation by PAR
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PAR1, 3 and 4 have been shown to directly couple with G12/13 (Offermanns et al. 1994). G12 and G13 have overlapping but distinct signalling roles (Suzuki et al. 2009). Evidence from conditional knockout mice (KOs) suggests that G13 is the subtype responsible for platelet shape change and aggregation responses in response to low and intermediate concentrations of thrombin, thromboxane and collagen. Platelets from G12 KOs were indistinguishable from wild-type, while those from mice with disrupted G13 had impaired shape change and aggregation responses, failed to form stable thrombi ex vivo, and exhibited a large increase in tailbleeding times (Moers et al. 2003). Both subtypes of G12/13 are unnecessary for platelet shape change and aggregation at higher agonist concentrations. The alpha-subunits of G12 and 13 bind RhoGEFs (guanine nucleotide exchange factors, which activate small G proteins) providing a path to Rho-mediated cytoskeletal responses that are involved in shape change in platelets and permeability and migration in endothelial cells.

Literature References
PubMed ID Title Journal Year
8290554 G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets

Schultz, G, Offermanns, S, Spicher, K, Laugwitz, KL

Proc Natl Acad Sci U S A 1994
Participants
Participates
Catalyst Activity

G protein-coupled receptor activity of Thrombin-activated PARs [plasma membrane]

Orthologous Events
Created
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