RhoG

RhoG (Ras homology Growth-related) (or ARGH) is a small (~21 kDa) monomeric GTP-binding protein (G protein), and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteinscite journal | author = Ridley AJ | title = Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking | journal = Trends Cell Biol. | volume = 16 | issue = 10 | pages = 522–9 | year = 2006 | month = October | pmid = 16949823 | doi = | url = | issn = ] and is encoded by the gene RHOG.cite web | title = Entrez Gene: RHOG ras homolog gene family, member G (rho G)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=391| accessdate = ]

Discovery

RhoG was first identified as a coding sequence which was upregulated in hamster lung fibroblasts upon stimulation with serum.cite journal | author = Vincent S, Jeanteur P, Fort P | title = Growth-regulated expression of rhoG, a new member of the ras homolog gene family | journal = Mol. Cell Biol. | volume = 12 | issue = 7 | pages = 3138–48 | year = 1992 | month = July | pmid = 1620121 | pmc = | url = | issn = ] Expression of RhoG in mammals is widespread and studies of its function have been carried out in fibroblasts,cite journal | author = Gauthier-Rouviere C, Vignal E, Meriane M, "et al" | title = RhoG GTPase Controls a Pathway That Independently Activates Rac1 and Cdc42Hs | journal = Mol. Biol. Cell | volume = 9 | issue = 6 | pages = 1379-94 | year = 1998 | month = June | pmid = 9614181 | pmc = | url = | issn = ] leukocytes,cite journal | author = Condliffe AM, Webb LM, Ferguson GJ, "et al"| title = RhoG regulates the neutrophil NADPH oxidase | journal = J. Immunol. | volume = 176 | issue = 9 | pages = 5314–20 | year = 2006 | month = May | pmid = 16621998 | url = | issn = ] neuronal cells, endothelial cellscite journal | author = van Buul JD, Allingham MJ, Samson T, "et al" | title = RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration | journal = J. Cell Biol. | volume = 178 | issue = 7 | pages = 1279-93 | year = 2007 | month = September | pmid = 17875742 | url = | issn = ] and HeLa cells. Despite its name, RhoG is more closely related to Rac and Cdc42 (72% and 62% sequence identity, respectively) than to Rho subfamily proteins and this is reflected in the fact that RhoG, Rac and Cdc42 share a subset of common binding partners.cite journal | author = Wennerberg K, Ellerbroek SM, Liu RY, "et al" | title = RhoG signals in parallel with Rac1 and Cdc42 | journal = J. Biol. Chem. | volume = 277 | issue = 49 | pages = 47810–7 | year = 2002 | month = December | pmid = 12376551 | doi = | url = | issn = ]

Function

Like most small G proteins RhoG is involved in a diverse set of cellular signalling mechanisms. In mammalian cells these include cell motility (through regulation of the actin cytoskeleton),cite journal | author = Katoh H, Hiramoto K, Negishi M | title = Activation of Rac1 by RhoG regulates cell migration | journal = J. Cell. Sci. | volume = 119 | issue = Pt 1 | pages = 56–65 | year = 2006 | month = January | pmid = 16339170 | doi = | url = | issn = ] gene transcription,cite journal | author = Vigorito E, Billadeu D, Savoy D, "et al"| title = RhoG regulates gene expression and the actin cytoskeleton in lymphocytes | journal = Oncogene | volume = 22 | issue = 3 | pages = 330-42 | year = 2003 | month = January | pmid = 12545154 | doi = | url = | issn = ] cite journal | author = Murga C, Zohar M, Teramoto H, Gutkind JS | title = Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-κB | journal = Oncogene | volume = 21 | issue = 2 | pages = 207–16 | year = 2002 | month = January | pmid = 11803464 | doi = | url = | issn = ] endocytosis,cite journal | author = Prieto-Sanchez RM, Berenjeno IM, Bustelo XR | title = Involvement of the Rho/Rac family member RhoG in caveolar endocytosis | journal = Oncogene | volume = 25 | issue = 21 | pages = 2961-73 | year = 2006 | month = May | pmid = 16568096 | pmc = | doi = | url = | issn = ] neurite outgrowth,cite journal | author = Katoh H, Yasui H, Yamaguchi Y, "et al" | title = Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells | journal = Mol. Cell Biol. | volume = 20 | issue = 19 | pages = 7378–87 | year = 2000 | month = October | pmid = 10982854 | pmc = | doi = | url = | issn = ] protection from anoikiscite journal | author = Yamaki N, Negishi M, Katoh H | title = RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism | journal = Exp. Cell Res. | volume = 313 | issue = 13 | pages = 2821–32 | year = 2007 | month = August | pmid = 17570359 | doi = | url = | issn = ] and regulation of the neutrophil NADPH oxidase.

Regulation of RhoG activity

As with all small G proteins RhoG is able to signal to downstream effectors when bound to GTP (Guanosine triphosphate) and unable to signal when bound to GDP (Guanosine diphosphate).Three classes of protein interact with RhoG to regulate GTP/GDP loading. The first are known as Guanine nucleotide exchange factors (GEFs) and these facilitate the exchange of GDP for GTP so as to promote subsequent RhoG-mediated signalling. The second class are known as GTPase activating proteins (GAPs) and these promote hydrolysis of GTP to GDP (via the intrinsic GTPase activity of the G protein) thus terminating RhoG-mediated signalling. A third group, known as Guanine nucleotide dissociation inhibitors (GDIs), inhibit dissociation of GDP and thus lock the G protein in its inactive state.GDIs can also sequester G proteins in the cytosol which also prevents their activation. The dynamic regulation of G protein signalling is necessarily complex and the 130 or more GEFs, GAPs and GDIs described thus far for the Rho family are considered to be the primary determinants of their spatiotemporal activity. There are a number of GEFs reported to interact with RhoG, although in some cases the physiological significance of these interactions has yet to be proven. Well characterised examples include the dual specificity GEF TRIO which is able to promote nucleotide exchange on RhoG and Raccite journal | author = Blangy A, Vignal, E, Schmidt S, "et al" | title = TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of RhoG | journal = J. Cell Sci. | volume = 113 | issue = Pt 4 | pages = 729–39 | year = 2000 | month = February | pmid = 10652265 | doi = | url = | issn = ] (via its GEFD1 domain) and also on RhoAcite journal | author = Bellanger J, Lazaro J, Diriong S, "et al" | title = The two guanine nucleotide exchange factor domains of Trio link the Rac1 and the RhoA pathways in vivo | journal = Oncogene | volume = 16 | issue = 2 | pages = 147-52 | year = 1998 | month = January | pmid = 9464532 | doi = | url = | issn = ] via a separate GEF domain (GEFD2). Activation of RhoG by TRIO has been shown to promote NGF-induced neurite outgrowth in PC12 cellscite journal | author = Estrach S, Schmidt S, Diriong S, "et al" | title = The Human Rho-GEF trio and its downstream target GTPase RhoG are involved in the NGF pathway, leading to neurite outgrowth | journal = Curr. Biol. | volume = 12 | issue = 4 | pages = 307-12 | year = 2002 | month = February | pmid = 11864571 | doi = | url = | issn = ] and phagocytosis of apoptotic cells in "C. elegans".cite journal | author = deBakker CD, Haney LB, Kinchen JM, "et al" | title = Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO | journal = Curr. Biol. | volume = 14 | issue = 24 | pages = 2208-16 | year = 2004 | month = December | pmid = 15620647 | doi = | url = | issn = ] Another GEF, known as SGEF (Src homology 3 domain-containing Guanine nucleotide Exchange Factor), is thought to be RhoG-specific and has been reported to stimulate macropinocytosis (internalisation of extracellular fluid) in fibroblastscite journal | author = Ellerbroek SM, Wennerberg K, Arthur T, "et al" | title = SGEF, a RhoG Guanine Nucleotide Exchange Factor that Stimulates Macropinocytosis | journal = Mol. Biol. Cell | volume = 15 | issue = 7 | pages = 3309-19 | year = 2004 | month = July | pmid = 15133129 | doi = | url = | issn = ] and apical cup assembly in endothelial cells (an important stage in leukocyte trans-endothelial migration). Other GEFs reported to interact with RhoG include Dbs, ECT2, VAV2 and VAV3.cite journal | author = Schuebel KE, Movilla N, Rosa JL, "et al" | title = Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2 | journal = EMBO J. | volume = 17 | issue = 22 | pages = 6608-21 | year = 1998 | month = November | pmid = 9822605 | doi = | url = | issn = ] cite journal | author = Movilla N and Bustelo XR| title = Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins | journal = Mol. Cell. Biol. | volume = 19 | issue = 11 | pages = 7870-85 | year = 1999 | month = November | pmid = 10523675 | doi = | url = | issn = ]

There have been very few interactions reported between RhoG and negative regulators of G protein function. Examples include IQGAP2 and RhoGDI3.cite journal | author = Zalcman G, Closson V, Camonis J, "et al" | title = 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 | journal = J. Biol. Chem. | volume = 271 | issue = 48 | pages = 30366-74 | year = 1996 | month = November | pmid = 8939998 | doi = | url = | issn = ]

ignalling downstream of RhoG

Activated G proteins are able to couple to multiple downstream effectors and can therefore control a number of distinct signalling pathways (a characteristic known as pleiotropy). The extent to which RhoG regulates these pathways is poorly understood thus far, however, one specific pathway downstream of RhoG has received much attention and is therefore well characterised. This pathway involves RhoG-dependent activation of Rac via the DOCK (dedicator of cytokinesis)-family of GEFs.cite journal | author = Cote J, Vuori K | title = GEF what? Dock180 and related proteins help Rac to polarize cells in new ways | journal = Trends Cell Biol. | volume = 17 | issue = 8 | pages = 383-93 | year = 2007 | month = August | pmid = 17765544 | doi = | url = | issn = ] This family is divided into four subfamilies (A-D) and it is subfamilies A and B that are involved in the pathway described here. Dock180, the archetypal member of this family, is seen as an atypical GEF in that efficient GEF activity requires the presence of the DOCK-binding protein ELMO (engulfment and cell motility)cite journal | author = Brugnera E, Haney L, Grimsley C, "et al" | title = Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex | journal = Nat. Cell Biol. | volume = 4 | issue = 8 | pages = 574-82 | year = 2002 | month = August | pmid = 12134158 | doi = | url = | issn = ] which binds RhoG at its N-terminus. The proposed model for RhoG-dependent Rac activation involves recruitment of the of ELMO/Dock180 complex to activated RhoG at the plasma membrane and this relocalisation, together with an ELMO-dependent conformational change in Dock180, is sufficient to promote GTP-loading of Rac.cite journal | author = Lu M, Kinchen JM, Rossman KL, "et al" | title = PH domain of ELMO functions "in trans" to regulate Rac activation via Dock180 | journal = Nat. Struct. Mol. Biol. | volume = 11 | issue = 8 | pages = 756-62 | year = 2004 | month = August | pmid = 15247908 | doi = | url = | issn = ] cite journal | author = Katoh H, Negishi M| title = RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo | journal = Nature | volume = 424 | issue = 6947 | pages = 461-64| year = 2003 | month = July | pmid = 12879077 | doi = | url = | issn = ] RhoG-mediated Rac signalling has been shown to promote neurite outgrowth and cell migration in mammalian cells as well as phagocytosis of apoptotic cells in "C. elegans".

Other proteins known to bind RhoG in its GTP-bound state include the microtubule-associated protein kinectin,cite journal | author = Vignal E, Blangy A, Martin M, "et al"| title = Kinectin is a key effector of RhoG microtubule-dependent cellular activity | journal = Mol. Cell Biol. | volume = 21 | issue = 23 | pages = 8022-34| year = 2001 | month = December | pmid = 11689693 | doi = | url = | issn = ] Phospholipase D1 and the MAP Kinase activator MLK3.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Taviaux SA, Vincent S, Fort P, Demaille JG |title=Localization of ARHG, a member of the RAS homolog gene family, to 11p15.5-11p15.4 by fluorescence in situ hybridization. |journal=Genomics |volume=16 |issue= 3 |pages= 788–90 |year= 1993 |pmid= 8325658 |doi=
*cite journal | author=Prieto-Sanchez RM, Bustelo XR |title=Structural Basis for the Signalling Specificity of RhoG and Rac1 GTPases. |journal=J. Biol. Chem. |volume=278 |issue= 39 |pages= 37916-25 |year= 2003 |pmid= 12805377 |doi=
*cite journal | author=Patel JC, Galan JE |title=Investigating the Function of Rho Family GTPases during "Salmonella"/Host Cell interactions. |journal=Meth. Enzym. |volume=439 |issue= |pages= 145-58 |year= 2008 |pmid= 18374162 |doi=
*cite journal | author=Patel JC, Galan JE |title=Differential activation and function of Rho GTPases during "Salmonella"-host cell interactions. |journal=J. Cell. Biol. |volume=175 |issue= 3 |pages= 453-63 |year= 2006 |pmid= 17074883 |doi=
*cite journal | author=Meller N, Merlot S, Guda C|title=CZH proteins: a new family of Rho-GEFs. |journal=J. Cell. Sci. |volume=118 |issue= Pt 21 |pages= 4937-46 |year= 2005 |pmid= 16254241 |doi=
*cite journal | author=Lu M, Kinchen JM, Rossman KL|title=A Steric-Inhibition Model for Regulation of Nucleotide Exhchange via the Dock180 Family of GEFs. |journal=Curr. Biol. |volume=15 |issue= 4 |pages= 371-77 |year= 2005 |pmid= 15723800 |doi=
*cite journal | author=Jankowski A, Zhu P, Marshall JG |title=Capture of an activated complex from the surface of live cells by affinity receptor chromatography. |journal=Anal. Biochem. |volume= |issue= |pages= |year= 2008 |pmid= 18601892 |doi=
*cite journal | author=Vigorito E, Bell S, Hebeis BJ, "et al" |title=Immunological Function in Mice Lacking the Rac-Related GTPase RhoG. |journal=Mol. Cell. Biol. |volume=24 |issue= 2 |pages= 719-29 |year= 2004 |pmid= 14701744 |doi=
*cite journal | author=Meller J, Vidali L, Schwartz MA|title=Endogenous RhoG is dispensible for integrin-mediated cell spreading but contributes to Rac-independent migration. |journal=J. Cell. Sci |volume=121 |issue= Pt 12 |pages= 1981-89 |year= 2008 |pmid= 18505794 |doi=
*cite journal | author=Miki T, Smith CL, Long JE, "et al." |title=Oncogene ect2 is related to regulators of small GTP-binding proteins. |journal=Nature |volume=362 |issue= 6419 |pages= 462–5 |year= 1993 |pmid= 8464478 |doi=
*cite journal | author=Le Gallic L, Fort P |title=Structure of the human ARHG locus encoding the Rho/Rac-like RhoG GTPase. |journal=Genomics |volume=42 |issue= 1 |pages= 157–60 |year= 1997 |pmid= 9177787 |doi=
*cite journal | author=Booden MA, Campbell SL, Der CJ |title=Critical but distinct roles for the pleckstrin homology and cysteine-rich domains as positive modulators of Vav2 signaling and transformation. |journal=Mol. Cell. Biol. |volume=22 |issue= 8 |pages= 2487–97 |year= 2002 |pmid= 11909943 |doi=
*cite journal | author=Skowronek KR, Guo F, Zheng Y, Nassar N |title=The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids. |journal=J. Biol. Chem. |volume=279 |issue= 36 |pages= 37895–907 |year= 2004 |pmid= 15199069 |doi=
*cite journal | author=Hiramoto K, Negishi M, Katoh H |title=Dock4 is regulated by RhoG and promotes Rac-dependent cell migration. |journal=Exp. Cell Res. |volume=312 |issue= 20 |pages= 4205–16 |year= 2007 |pmid= 17027967 |doi=
*cite journal | author=Gumienny TL, Brugnera E, Tosello-Trampont A "et al" |title=CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration |journal=Cell |volume=107 |issue= 1 |pages= 27-41 |year= 2001 |pmid= 11595183 |doi=
*cite journal | author=Kunisaki Y, Nishikimi A, Tanaka Y, "et al" |title=DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. |journal=J. Cell. Biol. |volume=174 |issue= 5 |pages= 647-52 |year= 2006 |pmid= 16943182 |doi=
*cite journal | author=Lu M, Ravichandran KS|title=Dock180-ELMO Cooperation in Rac Activation. |journal=Meth. Enzym. |volume=406 |issue= |pages= 388-402 |year= 2006 |pmid= 16472672 |doi=

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = no
update_citations = yes