title: Physiology and pathophysiology of proteinase-activated receptors (PARs): PAR-2-mediated proliferation of colon cancer cell.
abstract: 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.
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. mbori@md.okayama-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Hideo K
authors.initials: HK
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D044464:Receptor, PAR-2 / Q000502:physiology*
chemical_list: D044464:Receptor, PAR-2