Function and regulation of RhoE.
The three Rnd proteins, Rnd1, Rnd2 and RhoE/Rnd3, are a subset of Rho family proteins that are unusual in that they bind but do not hydrolyse GTP, and are therefore not regulated by the classical GTP/GDP conformational switch of small GTPases. Increased expression of each Rnd protein induces loss of stress fibres in cultured fibroblasts and epithelial cells, acting antagonistically to RhoA, which stimulates stress fibre formation. RhoE is farnesylated and localizes partly on membranes, including the Golgi and plasma membrane, and in the cytosol. RhoE inhibits RhoA signalling in part by binding to the RhoA-activated serine/threonine kinase ROCK I (Rho-associated kinase I), thereby preventing it from phosphorylating its targets. RhoE activity is itself regulated by phosphorylation by ROCK I on multiple sites. RhoE phosphorylation enhances its stability, leading to an increase in RhoE levels. In addition, phosphorylation reduces its association with membranes and correlates with its ability to induce loss of stress fibres. RhoE also acts independently of ROCK to inhibit cell cycle progression, in part by preventing translation of cyclin D1, and to inhibit transformation of fibroblasts by oncogenic H-Ras. RhoE is therefore a multifunctional protein whose localization and actions are regulated by phosphorylation.
Riento
K
K
Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House Street, London W1W 7BS, UK.
Villalonga
P
P
Garg
R
R
Ridley
A
A
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D010766:Phosphorylation
D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate