Activation of MAPK in fibroblasts by Treponema denticola major outer sheath protein.
The major outer sheath protein (Msp) of Treponema denticola induces Ca(2+) entry and actin reorganization in cultured fibroblasts, but the pathways by which Msp mediates these responses are not yet defined. We considered that Msp may activate protein kinases as a stress response that precedes actin remodelling. Phospho-kinase screens showed that Msp induced phosphorylation of multiple kinases in pathways that respond to extracellular agonists and regulate actin assembly. 34 kinases were significantly activated, including p38 and ERK 1/2. Accordingly, the expression and phosphorylation of p38 and ERK 1/2 in whole cell lysates were measured by immunoblotting and densitometry. Both kinases responded in a dose- and time-dependent manner to Msp exposure, were inhibited by SB202190 and U1026, respectively, and were unaffected by extracellular Ca(2+). These data indicate that T. denticola Msp may exert transient stress on fibroblasts through activation of MAP kinase pathways.
Jobin
Marie-Claude
MC
CIHR Group in Matrix Dynamics, Dental Research Institute, University of Toronto, Toronto, Ont., Canada. marieclaude.jobin@utoronto.ca
Virdee
Inderpreet
I
McCulloch
Christopher A
CA
Ellen
Richard P
RP
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D018272:Porins / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001426:Bacterial Proteins; D002070:Butadienes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D018272:Porins; D011725:Pyridines; C113580:U 0126; C099361:major outer sheath protein, Treponema; D011494:Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D002118:Calcium