血管平滑筋収縮のカルシウム感受性増加におけるFynチロシンキナーゼの重要性

抄録

Rho-kinase (ROK) is being regarded as the critical signaling molecule of the Ca²⁺-independent contraction of vascular smooth muscle (VSM). We recently identified that the sphingosylphosphorylcholine (SPC) induced Ca²⁺-independent contraction of VSM by activating ROK and that SPC activated ROK via activating Src family tyrosine kinase (Src-TK). Since VSM expresses Fyn and c-Src among Src-TK, we analysed which Src-TK is involved in this SPC/ROK-mediated Ca²⁺ sensitization. The inhibitors of Src-TK (PP1 and PP2) abolished all the reactions of Ca²⁺-independent contraction, activation of Src-TK and ROK, and tyrosine phosphorylation of p60 protein induced by SPC. SPC induced the translocation of Fyn from cytosol to the plasma membrane of VSM cells, but not that of c-Src. In order to examine directly the ability of Fyn to induce Ca²⁺-independent contraction, we made recombinant Fyn proteins using a baculovirus system. In beta-escin permeabilized VSM, constitutively active Fyn induced Ca²⁺-independent contraction which was inhibited by Y27632, while dominant negative Fyn inhibited the contraction induced by U46619+GTP. These findings suggest that Fyn tyrosine kinase plays a pivotal role in the SPC-induced and ROK-mediated Ca²⁺-independent contraction. [J Physiol Sci. 2006;56 Suppl:S67]