抄録
Actin stress fibers play important roles in various cellular functions, including cell motility, morphogenesis and tumorigenicity. It is known that Rho and its effector Rho-kinase (ROCK) play a critical role in stress fiber formation and are implicated to be involved in the stress fiber formation induced by sphingosylphosphorylcholine (SPC) and lysophosphatidic acid (LPA). However, except for Rho, the upstream mediator(s) for the ROCK-mediated stress fiber formation is still unknown. In this study, we provide the first direct evidence that Fyn, a member of Src family tyrosine kinase, acts as a novel signaling molecule in the actin stress fiber formation in NIH3T3 fibroblasts. Either LPA or SPC activated Fyn and induced stress fiber formation, which was blocked by pharmacological inhibition and gene silencing of Fyn, or dominant negative Fyn. Overexpressed constitutively active Fyn colocalized with focal adhesion kinase at the both ends of F-actin bundles and triggered stress fiber formation, only the latter of which was abolished by ROCK inhibition. SPC, but not LPA, also induced another form of actin cytoskeleton reorganization, filopodia-like protrusion formation, which was not mediated by Fyn and ROCK. Thus, Fyn appears to act downstream of LPA and SPC to specifically stimulate stress fiber formation mediated by ROCK in fibroblasts. [J Physiol Sci. 2008;58 Suppl:S52]
