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Last update 23 Jan 2025

RHOG

Last update 23 Jan 2025

Basic Info

Synonyms

ARHG, MGC125835, MGC125836

+ [3]

Introduction

Required for the formation of membrane ruffles during macropinocytosis. Plays a role in cell migration and is required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB and ARHGEF26/SGEF, which induces cytoskeleton rearrangements and promotes bacterial entry.

Drugs associated with RHOG

WO2024121426

Patent Mining

Target

RHOG

Mechanism-

Active Org.

Das CeMM - Forschungszentrum für Molekulare Medizin GmbH

Originator Org.

Das CeMM - Forschungszentrum für Molekulare Medizin GmbH

Active Indication

Hemic and Lymphatic Diseases [+2]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RHOG

100 Translational Medicine associated with RHOG

0 Patents (Medical) associated with RHOG

285

Literatures (Medical) associated with RHOG

01 Jan 2025·Journal of Biological Chemistry

Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division

Article

Author: Yasutake, Ryuji ; Kuwajima, Hiroki ; Yuki, Ryuzaburo ; Nakayama, Yuji ; Saito, Youhei ; Tanaka, Junna

Ephexin proteins are guanine nucleotide exchange factors for the Rho GTPases. We reported that Ephexin4 regulates M-phase progression downstream of phosphorylated EphA2, a receptor-type tyrosine kinase, through RhoG activation; however, the regulation of Ephexin4 during M phase remains unknown. In this study, a novel Ephexin4 phosphorylation site was identified at Ser41, exclusively in M phase. Ephexin4 knockdown prolonged the duration of M phase by activating the spindle assembly checkpoint, at which BubR1 was localized at the kinetochores of the misaligned chromosomes. This delay was alleviated by re-expression of wild-type, but not S41A Ephexin4. The Ephexin4 knockdown caused chromosome misalignment and reduced the RhoG localization to the plasma membrane. These phenotypes were rescued by re-expression of wild-type and phospho-mimic S41E mutant, but not the S41A mutant. Consistently, S41E mutant enhanced active RhoG levels, even in the interphase. Regardless of the Ephexin4 knockdown, active RhoG-G12V was localized at the plasma membrane. Furthermore, Ephexin4 knockdown exacerbated vincristine-induced chromosome misalignment, which was prevented by re-expressing the wild-type but not S41A Ephexin4. Overexpression of wild-type and S41E mutant, but not S41A mutant, resulted in an increased number of Madin-Darby canine kidney (MDCK) cysts with cells inside the lumen, indicating disruption of epithelial morphogenesis by deregulating Ephexin4/RhoG signaling in cell division. Our results suggest that Ephexin4 undergoes phosphorylation at Ser41 in cell division, and the phosphorylation is required for chromosome alignment through RhoG activation. Combined with mitosis-targeting agents, inhibition of Ephexin4 phosphorylation may represent a novel strategy for cancer chemotherapy.

27 Nov 2024·Journal of Leukocyte Biology

RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis

Article

Author: Eitzen, Gary ; Zhang, Eric L ; Van Petten, Jennifer

AbstractMast cells are hematopoietic-derived immune cells that possess numerous cytoplasmic granules containing immune mediators such as cytokines and histamine. Antigen stimulation triggers mast cell granule exocytosis, releasing granule contents in a process known as degranulation. We have shown that Rho GTPase signaling is an essential component of granule exocytosis, however, the proteins that regulate Rho GTPases during this process are not well defined. Here we examined the role of Rho guanine-nucleotide dissociation inhibitors (RhoGDIs) in regulating Rho GTPase signaling using RBL-2H3 cells as a mast cell model. We found that RBL-2H3 cells express two RhoGDI isoforms which are primarily localized to the cytosol. Knockdown of RhoGDI1 and RhoGDI2 greatly reduced the levels of all Rho GTPases tested: RhoA, RhoG, Rac1, Rac2, and Cdc42. The reduction in Rho GTPase levels was accompanied by an increase in their membrane-localized fraction and an elevation in the levels of active Rho GTPases. All RhoGDI knockdown strains had altered resting cell morphology, although each strain was activation competent when stimulated. Live cell imaging revealed that the RhoGDI1/2 double knockdown (DKD) strain maintained its activated state for prolonged periods of time compared to the other strains. Only the RhoGDI1/2 DKD strain showed a significant increase in granule exocytosis. Conversely, RhoGDI overexpression in RBL-2H3 cells did not noticeably affect Rho GTPases or degranulation. Based on these results, RhoGDIs act as negative regulators of Rho GTPases during mast cell degranulation, and inhibit exocytosis by sequestering Rho GTPases in the cytosol.

01 Oct 2024·Journal of Cell Science

The Scribble–SGEF–Dlg1 complex regulates E-cadherin and ZO-1 stability, turnover and transcription in epithelial cells

Article

Author: Ali, Nabaa ; Rabino, Agustin ; Awadia, Sahezeel ; Edson, Amber ; Garcia-Mata, Rafael

ABSTRACTSGEF (also known as ARHGEF26), a RhoG specific GEF, can form a ternary complex with the Scribble polarity complex proteins Scribble and Dlg1, which regulates the formation and maintenance of adherens junctions and barrier function of epithelial cells. Notably, silencing SGEF results in a dramatic downregulation of both E-cadherin and ZO-1 (also known as TJP1) protein levels. However, the molecular mechanisms involved in the regulation of this pathway are not known. Here, we describe a novel signaling pathway governed by the Scribble–SGEF–Dlg1 complex. Our results show that the three members of the ternary complex are required to maintain the stability of the apical junctions, ZO-1 protein levels and tight junction (TJ) permeability. In contrast, only SGEF is necessary to regulate E-cadherin levels. The absence of SGEF destabilizes the E-cadherin–catenin complex at the membrane, triggering a positive feedback loop that exacerbates the phenotype through the repression of E-cadherin transcription in a process that involves the internalization of E-cadherin by endocytosis, β-catenin signaling and the transcriptional repressor Slug (also known as SNAI2).

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RHOG

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