Tec/Bmx non-receptor tyrosine kinases are involved in regulation of Rho and serum response factor by Gα12/13

A transient transfection system was used to identify regulators and effecters for Tec and Bmx, members of the Tec non-receptor tyrosine kinase family. We found that Tec and Bmx activate serum response factor (SRF), in synergy with constitutively active a subunits of the G12 family of GTP-binding proteins, in transiently transfected NIH 3T3 cells. The SRF activation is sensitive to C3, suggesting the involvement of Rho, The kinase and Tec homology (TH) domains of the kinases are required for SRF activation. In addition, kinase-deficient mutants of Bmx are able to inhibit G alpha 13- and G alpha 12-induced SRF activation, and to suppress thrombin-induced SRF activation in cells lacking G alpha q/11, where thrombin's effect is mediated by G12/13 proteins. Moreover, expression of G alpha 12 and G alpha 13 stimulates autophosphorylation and transphosphorylation activities of Tec. Thus, the evidence indicates that Tec kinases are involved in G alpha 12/13-induced, Rhomediated activation of SRF. Furthermore, Src, which was previously shown to activate kinase activities of Tec kinases, activates SRF predominantly in Rho-independent pathways in 3T3 cells, as shown by the fact that C3 did not block Src-mediated SRF activation. However, the Rho-dependent pathway becomes significant when Tec is overexpressed.