Regulation of Rho-GTPases

 

    The GTPases of the Rho family control almost every aspect of cell behavior, including cell migration, cell-cell adhesion, cell polarity, contractility, invasion, proliferation and differentiation, and gene transcription. Rho GTPases function as a link between surface receptors and the actin cytoskeleton. Activation of Rho proteins is mediated by guanine-nucleotide exchange factors (GEFs), which catalyze the exchange of GDP for GTP. However, both the identity of Rho-GEFs involved in these processes and the mechanisms for their regulation are virtually unknown.

 

                            

        My long term objective is to elucidate the mechanisms that control the targeting and regulated activation of Rho-GTPases. These processes have been shown to play essential roles both in normal cell function, as well as in abnormal cell behavior such as atherosclerosis, hypertension, restenosis, inflammation and hypertension .    

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In the past several years I have focused my research in two fundamental questions of Rho GTPase biology:

 

1) How are Rho-GEF proteins regulated?

Given the multiplicity of molecules that converge to regulate the activity of Rho GTPases and the diversity of their effectors, it is surprising that Rho proteins can exquisitely orchestrate the appropriate cellular response to each extracellular cue. Recent studies have demonstrated that the interaction of GEFs with scaffolding proteins might represent a general mechanism by which GEFs can control the selection of signal outputs upon Rho GTPase activation 

2) What specific Rho-GEFs are responsible for Rho activation downstream of known pathways?

 

 

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