Research article
The Fer tyrosine kinase regulates interactions of Rho GDP-Dissociation Inhibitor α with the small GTPase Rac
- † Equal contributors
1 Section of Molecular Carcinogenesis, Division of Hematology/Oncology, The Saban Research Institute of Childrens Hospital Los Angeles, CA 90027, USA
2 Leukemia Research Program, Childrens Hospital Los Angeles, CA 90027, USA
3 Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI 48105, USA
4 INSERM, UMR 891, Centre de Recherche en Cancérologie de Marseille, Laboratoire de Signalisation, Hématopoïèse et Mécanismes de l'Oncogenèse, Marseille, France
5 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
BMC Biochemistry 2010, 11:48 doi:10.1186/1471-2091-11-48
Published: 1 December 2010Abstract
Background
RhoGDI 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.
Results
We 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.
Conclusions
These results identify tyrosine phosphorylation of RhoGDIα by Fer as a mechanism to regulate binding of RhoGDIα to Rac.
