Disease relevance of RHOG

• Significantly higher levels of Rho-C and Rho-G were seen in patients who died of breast cancer than in those who remained disease free [1].
• In addition, we report that SopB stimulates cellular responses by activating SH3-containing guanine nucleotide exchange factor (SGEF), an exchange factor for RhoG, which we found plays a central role in the actin cytoskeleton remodeling stimulated by Salmonella [2].
• We show here that induction of Shigella entry foci is controlled by the Cdc42, Rac and Rho GTPases, but not by RhoG [3].
• The analysis revealed that the 52 kDa FK506 binding protein, Rho G-protein dissociation inhibitor (RhoGDI), and glyoxalase I are found to be uniquely overexpressed in invasive human ovarian cancer when compared to the LMP form of this cancer [4].

High impact information on RHOG

• Kinectin is a key effector of RhoG microtubule-dependent cellular activity [5].
• We have identified a novel role for RhoG in signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor agonists [6].
• By screening a cDNA library of a mouse macrophage cell line, we identified two small GTPase family members (RhoG and Rab5) that enhanced the engulfment of apoptotic cells [7].
• Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO [8].
• RESULTS: Here, we define a conserved signaling module involving the small GTPase RhoG and its exchange factor TRIO, which functions upstream of ELMO/Dock180/Rac during engulfment [8].

Biological context of RHOG

• Hence, these results implicate RhoG in leukocyte trafficking and the control of gene expression induced in response to antigen encounter [9].
• Here we investigated the role of RhoG in cell migration [10].
• DNA array analysis revealed that expression of genes such as the RhoG and D4-GDI genes was down-regulated in TEL-overexpressing cells, while that of the representative growth-related genes such as the c-myc, c-fos and c-jun genes was not remarkably changed [11].

Anatomical context of RHOG

• RhoG, kinectin, and kinesin colocalize in REF-52 and COS-7 cells, mainly in the endoplasmic reticulum but also in lysosomes [5].
• Finally, transient transduction of a tat-tagged Rac1(17N) dominant-negative fusion protein inhibited the induction of lamellipodia by the Rac-specific activator, Tiam1, but not by activated RhoG [12].
• RhoG, a member of the Rho family of GTPases, has been implicated as a regulator of the actin cytoskeleton [9].
• In this study, we show a novel function for the small GTPase RhoG on the regulation of the interferon-gamma promoter and nuclear factor of activated T cells (NFAT) gene transcription in lymphocytes [9].
• RhoG, a member related to Rac and Cdc42Hs, is activated at the transcriptional level in the mid-G1 phase of stimulated fibroblasts [13].

Associations of RHOG with chemical compounds

• The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor [14].
• The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids [15].
• Our data suggest a role for the phosphoinositide 3-kinase, PI 3-kinase, in modulating the Trio/RhoG signaling pathway [15].
• The PGE(2) level of irradiated cells was higher than in controls (1512 +/- 157.5 vs. 973.7 +/- 54.2 rhog PGE(2)/mL; p < 0.005, n = 4) while cells irradiated in the presence of NS-398 had reduced PGE(2) levels (218.8 +/- 80.1 rhog PGE(2)/mL; p < 0.005; n = 4) [16].
• Steady-state PK of octreotide 20 mg/28 d suggested a C(mean) of 1216 rhog/mL (range, 1065-1585) with low fluctuation index (43%) [17].

Regulatory relationships of RHOG

• We conclude that RhoG activates Rac1 through Elmo and Dock180 to control cell morphology [14].
• Full-length SGEF activated RhoG, but not Rac, when expressed in fibroblasts [18].
• Dock4 is regulated by RhoG and promotes Rac-dependent cell migration [19].

Other interactions of RHOG

• RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG [20].
• SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis [18].
• Scanning electron microscopy of fibroblasts demonstrated that SGEF induced dorsal ruffles that were morphologically similar to those generated by constitutively active RhoG, but not constitutively active Rac1 [18].
• Node-positive tumors have significantly higher levels of Rho-C and Rho-G, and lower levels of Rho-GDI and Rho-GDI-gamma transcripts, than do node-negative tumors [1].
• Trio contains two DH/PH tandem domains that respectively activate the small GTPases RhoG/Rac and RhoA [21].

Analytical, diagnostic and therapeutic context of RHOG

• Localization of ARHG, a member of the RAS homolog gene family, to 11p15.5-11p15.4 by fluorescence in situ hybridization [22].
• Interleukin-6 concentrations were greater in the control group than the propofol group 4 hours after clamp release (289.1 [165.2-561] rhog/mL v 153.2 (58.2-280.3) rhog/mL, respectively, p = 0.003) [23].

References