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.
Nishibori
Masahiro
M
Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. mbori@md.okayama-u.ac.jp
Mori
Shuji
S
Takahashi
Hideo K
HK
D000818:Animals; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D044464:Receptor, PAR-2 / Q000502:physiology*
D044464:Receptor, PAR-2