The Fer tyrosine kinase regulates interactions of Rho GDP-Dissociation Inhibitor α with the small GTPase Rac

摘要

Background: RhoGDI proteins are important regulators of the small GTPase Rac, because they shuttle Rac from thecytoplasm to membranes and also protect Rac from activation, deactivation and degradation. How the bindingand release of Rac from RhoGDI is regulated is not precisely understood.Results: We report that the non-receptor tyrosine kinase Fer is able to phosphorylate RhoGDIa and form α directprotein complex with it. This interaction is mediated by the C-terminal end of RhoGDIα. Activation of Fer byreactive oxygen species caused increased phosphorylation of RhoGDIα and pervanadate treatment furtheraugmented this. Tyrosine phosphorylation of RhoGDIα by Fer prevented subsequent binding of Rac to RhoGDIa,but once a RhoGDIα-Rac complex was formed, the Fer kinase was not able to cause Rac release through tyrosinephosphorylation of preformed RhoGDIα-Rac complexes.Conclusions: These results identify tyrosine phosphorylation of RhoGDIa by Fer as α mechanism to regulatebinding of RhoGDIα to Rac.