Rat Protease Activated Receptor 2 ELISA Kit

G-protein coupled receptors (GPCRs) evolved as specialized sensors of the extracellular environment. Comprising the largest family of cell surface receptors, GPCRs are common therapeutic targets. Over the last 25 years, several GPCRs have been observed at the cell nucleus, suggesting the presence of intracrine GPCR signaling beyond the plasma membrane. Yet specific physiological functions of nuclear GPCRs had not been reported, until lately. We recently uncovered distinct but complementary angiogenic roles of F2rl1 (formerly known as PAR2) depending on its subcellular localization at the plasma membrane or at the nucleus. Targeting subcellular compartments to improve drug selectivity may therefore inspire novel therapeutic strategies for transmembrane receptors.

Activation of the blood coagulation cascade leads to fibrin deposition and platelet activation that are required for hemostasis. However, aberrant activation of coagulation can lead to thrombosis. Thrombi can cause tissue ischemia, and fibrin degradation products and activated platelets can enhance inflammation. In addition, coagulation proteases activate cells by cleavage of PARs (protease-activated receptors), including PAR1 and PAR2. Direct oral anticoagulants have recently been developed to specifically inhibit the coagulation proteases FXa (factor Xa) and thrombin. Administration of these inhibitors to wild-type mice can be used to determine the roles of FXa and thrombin in different inflammatory diseases. These results can be compared with the phenotypes of mice with deficiencies of either Par1 (F2r) or Par2 (F2rl1). However, inhibition of coagulation proteases will have effects beyond reducing PAR signaling, and a deficiency of PARs will abolish signaling from all proteases that activate these receptors. We will summarize studies that examine the roles of coagulation proteases, particularly FXa and thrombin, and PARs in different mouse models of inflammatory disease. Targeting FXa and thrombin or PARs may reduce inflammatory diseases in humans.