In this issue, Sevigny and colleagues demonstrate that a protease-activated receptor 1 (PAR1)-PAR2 heterodimer regulates vascular smooth muscle cell (VSMC) hyperplasia following vascular injury 1. PARs belong to a family of G-protein coupled receptors that are proteolytically activated by a variety of proteases 2, 3. Cleavage of PARs results in intracellular signaling mediated by activation of various G proteins including G12/13, Gq, and Gi 2, 4-6. The PAR family consists of 4 members, PAR1-PAR4, with PARs 1, 3, and 4 being primarily activated by thrombin, while PAR2 is activated by trypsin and tryptase 2, 3. PAR1, originally identified as a thrombin receptor on platelets, is widely expressed and has been shown to regulate a multitude of physiological processes including platelet activation 7, 8, regulation of the endothelial cell barrier function 9, and proliferation and de-differentiation of VSMCs 10, 11. In addition to PAR1, these cells express other PARs 6. Importantly members of PAR family can physically interact and signal as functional heterodimers in order to regulate cell growth, proliferation and activation 12-15. PAR1 for example, has been shown to trans-activate PAR2 in human endothelial and COS-7 cells 15, while on the platelet PAR1 may heterodimerize with PAR4
Recommended CitationPawlinski, Rafal and Holinstat, Michael, "We can do it together: PAR1/PAR2 heterodimer signaling in VSMCs." (2011). Department of Medicine Faculty Papers. Paper 66.