Selective activation of small GTPase RhoA by tyrosine kinase Etk through its pleckstrin homology domain.

Etk/Bmx is a member of the Btk family tyrosine kinase, which contains an N-terminal pleckstrin homology domain. Etk has been shown to play a pivotal role in the regulation of various cellular processes including differentiation, apoptosis, and cell motility. Here we present evidence that Etk is a modulator of the small GTPase RhoA. Etk and RhoA both are translocated to the plasma membrane and can form a complex upon serum stimulation in C2C12 cells. Etk interacts with RhoA but not other closely related small GTPases such as Cdc42 and Rac1, suggesting a specific modulation of RhoA by Etk. Our results demonstrate that Etk activates RhoA and enhances Rho-mediated stress fiber formation and transcription activity in a pleckstrin homology domain-dependent manner. Furthermore, Etk disrupts the interaction between RhoA and Rho-GDI (guanine nucleotide dissociation inhibitor) and promotes the membrane translocation of RhoA. Our data suggest that Etk plays an important role in regulation of RhoA-mediated signaling.