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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Physiology and pathophysiology of proteinase-activated receptors (PARs): PAR-2-mediated proliferation of colon cancer cell.

Proteinase-activated receptor-2 ( PAR-2) has been demonstrated to be highly expressed in the gastrointestinal tract. In the present minireview, we summarize the effects of PAR-1 and PAR-2 stimulation using their activating peptides and agonist proteinases on the calcium signaling and the cell proliferation in DLD-1 cell, a human colon cancer cell line. PAR-2 but not PAR-1 stimulation induced the enhancement of cell proliferation, whereas both PAR-1 and PAR-2 stimulation induced the transient increase in [Ca(2+)](i). PAR-2 stimulation induced the phosphorylation of MEK1/2 and ERK1/2, but PAR-1 stimulation did not. The inhibition of MEK1/2 by PD98059 completely abolished the proliferative response to PAR-2 stimulation. Thus, MEK- ERK activation plays major role in the PAR-2-mediated proliferative response. The coupling of PARs to calcium signaling and MEK- ERK activation may be independent, and varied dependent on cell types.[1]


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