抄録
Stress fiber formation plays an important role in the regulation of the cell structure and motility. At present, Rho GTPase and its effecter Rho-kinase (ROK) are known to play a critical role in stress fiber formation. However, the upstream signaling pathway for the activation of Rho GTPase and ROK remains to be elucidated. We previously showed that sphingosylphosphorylcholine (SPC) and Src family tyrosine kinase (Src-TK) are the upstream mediators of ROK-mediated Ca2+ sensitization of vascular smooth muscle contraction. Here we found that SPC induced stress fiber formation in NIH3T3 fibroblasts, which was assessed by the confocal images of the F-actin staining with phalloidin. The SPC-induced stress fiber formation was abolished by a ROK inhibitor (Y27632) and was partially blocked by Src-TK inhibitors (PP1, PP2), but not by their inactive analogue (PP3). In contrast, the stress fiber formation induced by its well-known stimulant, lysophosphatidic acid (LPA) was blocked by Y27632, but not by PP1 or PP2, although SPC and LPA induced stress fiber formation to the same extent. In addition, SPC, but not LPA, induced the formation of filopodia-like protrusions, which were not blocked by PP1, PP2, and Y27632. These findings suggest that SPC and LPA stimulate the ROK-mediated stress fiber formation in fibroblasts through the Src-TK-dependent and independent pathway, respectively. The formation of filopodia-like protrusions induced by SPC, but not by LPA, was not mediated by the both kinases and its mechanism is unknown. [Jpn J Physiol 55 Suppl:S72 (2005)]
