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. Author manuscript; available in PMC: 2017 May 1.
Published in final edited form as: Curr Opin Hematol. 2016 May;23(3):274–279. doi: 10.1097/MOH.0000000000000232

Fig. 2. Model of thrombin-activated PAR1 induction of non-canonical p38 MAP kinase signaling.

Fig. 2

Activation of PAR1 by α-thrombin (α-Th) promotes rapid coupling to heterotrimeric G proteins comprised of α and βγ subunits. Activated PAR1 is rapidly phosphorylated and ubiquitinated, the latter of which is mediated by the NEDD4-2 E3 ubiquitin ligase. Ubiquitination of activated PAR1 induces recruitment of TAB2 on endosomes. TAB2 associates with TAB1, which binds to p38 MAP kinase promoting autophosphorylation and activation following thrombin stimulation. Intriguingly, TAB1 protein is stabilized following recruitment to activated PAR1-TAB2-p38 MAP kinase signaling complex. Importantly, PAR1-stimulated non-canonical 38 MAP kinase activation causes a significant increase in endothelial barrier permeability.

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