Abstract
BackgroundRhoGDI proteins are important regulators of the small GTPase Rac, because they shuttle Rac from the cytoplasm to membranes and also protect Rac from activation, deactivation and degradation. How the binding and release of Rac from RhoGDI is regulated is not precisely understood.ResultsWe report that the non-receptor tyrosine kinase Fer is able to phosphorylate RhoGDIα and form a direct protein complex with it. This interaction is mediated by the C-terminal end of RhoGDIα. Activation of Fer by reactive oxygen species caused increased phosphorylation of RhoGDIα and pervanadate treatment further augmented this. Tyrosine phosphorylation of RhoGDIα by Fer prevented subsequent binding of Rac to RhoGDIα, but once a RhoGDIα-Rac complex was formed, the Fer kinase was not able to cause Rac release through tyrosine phosphorylation of preformed RhoGDIα-Rac complexes.ConclusionsThese results identify tyrosine phosphorylation of RhoGDIα by Fer as a mechanism to regulate binding of RhoGDIα to Rac.
Highlights
RhoGDI proteins are important regulators of the small GTPase Rac, because they shuttle Rac from the cytoplasm to membranes and protect Rac from activation, deactivation and degradation
To investigate if the deregulated Bcr/Abl tyrosine kinase, similar to oncogenic Src [7], is able to modify RhoGDIa, we performed an immunocomplex kinase assay with cells expressing Bcr/Abl or with Fer, a non-receptor tyrosine kinase related to Abl, in the presence of added recombinant GST-RhoGDIa or control GST
There was a prominent signal of phosphorylated RhoGDIa in the sample expressing Fer (Figure 1A right panel)
Summary
RhoGDI proteins are important regulators of the small GTPase Rac, because they shuttle Rac from the cytoplasm to membranes and protect Rac from activation, deactivation and degradation. Racs are post-translationally modified by the removal of C-terminal amino acid residues, followed by the attachment of a lipid moiety in the form of a geranyl-geranyl group [1]. Because of this modification, mature Rac proteins are lipophilic and are only present in the cytosol when bound to the chaperone and transport protein RhoGDI. A recent study showed that Rho proteins compete for binding to a limited pool of RhoGDI, which, once it has bound them, provides stabilization and protection from degradation [2]
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