Regulation of Leukaemia Associated Rho GEF (LARG/ARHGEF12)

ABSTRACT

The Ras homologous (Rho) protein family of GTPases (RhoA, RhoB and RhoC) are the members of the Ras superfamily and regulate cellular processes such as cell migration, proliferation, polarization, adhesion, gene transcription and cytoskeletal structure. Rho GTPases function as molecular switches that cycle between GTP-bound (active state) and GDP-bound (inactive state) forms. Leukaemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) that activates RhoA subfamily GTPases by promoting the exchange of GDP for GTP. LARG is selective for RhoA subfamily GTPases and is an essential regulator of cell migration and invasion. Here, we describe the mechanisms by which LARG is regulated to facilitate the understanding of how LARG mediates functions like cell motility and to provide insight for better therapeutic targeting of these functions.

KEYWORDS:

• ARHGEF12
• GTPase
• LARG
• migration
• Rho
• RhoGef
• signal transduction

Attribution of Authorship

N.Z.G. compiled relevant works and wrote the initial draft. N.Z.G., M.L.M. and J.W.R. wrote and revised the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by NIH R01HD091162 (to M.L.M) and the B.H. and Alice C. Beams Endowed Professorship in Cancer Research (to J.W.R.);National Institutes of Health [R01HD091162].