title: Selective activation of small GTPase RhoA by tyrosine kinase Etk through its pleckstrin homology domain.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Oekyung
authors.initials: O
authors.lastname: Kim
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D010750:Phosphoproteins; C039077:platelet protein P47; C492367:BMX protein, human; D011505:Protein-Tyrosine Kinases; D020742:rhoA GTP-Binding Protein