GTP‐binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo

Abstract

SummaryRho/Rac proteins constitute a subgroup of the Ras superfamily of GTP hydrolases. Although originally implicated in the control of cytoskeletal events, it is currently known that these GTPases coordinate diverse cellular functions, including cell polarity, vesicular trafficking, the cell cycle and transcriptomal dynamics. In this review, we will provide an overview on the recent advances in this field regarding the mechanism of regulation and signaling, and the roles in vivo of this important GTPase family.

Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation

“…Signals emanating from membrane receptors frequently lead to the activation of more than one GTPase, thus ensuring a rapid and efficient pleiotropic response (9). However, the kinetics of activation of these GTPases often differs significantly from one another.…”

“…It is believed that the functional specificity of the GTPases is provided by the interaction that they establish with specific guanine nucleotide exchange factors and effector molecules (9). Thus, there is an increasing interest to identify the protein partners with which GTPases associate.…”

“…Examples include receptors with intrinsic tyrosine kinase activity such as EGF receptor (2)(3)(4) and PDGF receptor (5,6) or other types such as G protein-coupled receptors (7,8). In their active configuration, GTPases interact with downstream effector molecules to promote a variety of biological responses (9). GTPases of the Rho family are best known for controlling the appropriate actin cytoskeleton reorganization in response to extracellular signals, although their implication in additional biological processes such as gene expression regulation, cell polarity, and cell migration has also been reported (1).…”

CdGAP is required for transforming growth factor β- and Neu/ErbB-2-induced breast cancer cell motility and invasion

“…The Rho subfamily of small GTPases, including RhoA, Cdc42 and Rac1, have important roles in the regulation of cell migration and invasion, cell polarity, vesicular trafficking, cell cycle progression, apoptosis and cancer (Titus et al, 2005;Bustelo et al, 2007;Karlsson et al, 2009;Tybulewicz and Henderson, 2009). Rho proteins cycle between an active GTP-bound state and an inactive GDP-bound state.…”

Mutations récurrentes des gènesRHOAetFYNdans les lymphomes T périphériques

“…La surexpression de RHOA G17V a à un état actif lié au GTP. L'équilibre entre ces deux conformations est régulé par l'activité des facteurs d'échange de guanine (GEF) qui catalysent la dissociation du GDP et le chargement en GTP et donc activent RHOA, et par celle des protéines activatrices de GTPases (GAP), qui stimulent l'hydrolyse du GTP en GDP et donc inactivent RHOA [8][9][10] ( Figure 2B). RHOA est impliquée dans nombre de processus cellulaires via l'activation de voies de signalisation variées [11] (Figure 2C).…”