Fig. 3.

Involvement of matrix metalloproteinases in PAR-1 mediated phosphorylation of the Smad2 linker region in human vascular smooth muscle cells. PAR-1 transactivation of the TGFBR1 leads to the phosphorylation of Smad2 in the carboxy terminus. PAR-1 transactivation of the EGFR occurs via the stimulation of MMPs. PAR-1 mediated phosphorylation of the Smad2 in the linker region is blocked by MMP inhibitor. Note carboxy terminal phosphorylation of Smad2 is not blocked by MMP antagonist indicating that MMPs are not involved in PAR-1 mediated TGFBR1 transactivation. Hence we postulate that PAR-1 mediated Smad2 linker region phosphorylation occurs via the transactivation of the EGFR