Stimulation of fibroblast proliferation by the plant cysteine protease CMS2MS2 is independent of its proteolytic activity and requires ERK activation.
The cysteine protease CMS2MS2 from Carica candamarcensis latex has been shown to enhance proliferation of L929 fibroblast and to activate the extracellular signal-regulated protein kinase (ERK). In experiments with CMS2MS2 irreversibly inhibited by E-64, the proliferative effect on fibroblasts remains unaffected. ERK phosphorylation mediated by CMS2MS2 was abolished in the presence of PD 98059 or U0126, both MAPK cascade inhibitors. In addition, these inhibitors suppress the mitogenic activity of intact CMS2MS2 or CMS2MS2-E-64. Furthermore, ERK phosphorylation and the mitogenic effect are partially suppressed by a phospholipase C (PLC) inhibitor. These data suggest that the mitogenic effect of CMS2MS2 on fibroblasts is independent of its proteolytic activity, requires ERK phosphorylation, and involves activation of PLC.
Gomes
Marco Túlio R
MT
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, CEP 31270-901, Brazil. mtrgomes@icb.ufmg.br
Turchetti
Andréia P
AP
Lopes
Miriam T P
MT
Salas
Carlos E
CE
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D029441:Carica / Q000201:enzymology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D057056:Cysteine Proteases / Q000494:pharmacology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology*; D005419:Flavonoids / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D002070:Butadienes; D005419:Flavonoids; D008934:Mitogens; D009570:Nitriles; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010738:Type C Phospholipases; D057056:Cysteine Proteases; D007930:Leucine; C024974:E 64; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one