Activation of MAPK in fibroblasts by Treponema denticola major outer sheath protein

Abstract

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.