Gene Symbol: ARHGEF11
Description: Rho guanine nucleotide exchange factor 11
Alias: GTRAP48, PDZ-RHOGEF, rho guanine nucleotide exchange factor 11, Rho guanine exchange factor (GEF) 11, Rho guanine nucleotide exchange factor (GEF) 11, RhoA-specific guanine nucleotide exchange factor, RhoGEF glutamate transport modulator, glutamate transporter EAAT4-associated protein 48
Species: human
Products:     ARHGEF11

Top Publications

  1. Barac A, Basile J, Vazquez Prado J, Gao Y, Zheng Y, Gutkind J. Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor. J Biol Chem. 2004;279:6182-9 pubmed
    ..Here we found that a member of the RGL-containing family of Rho guanine exchange factors, PDZ RhoGEF, which, together with LARG and p115RhoGEF, links the G(12/13) family of heterotrimeric G proteins to Rho ..
  2. Rümenapp U, Blomquist A, Schwörer G, Schablowski H, Psoma A, Jakobs K. Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member. FEBS Lett. 1999;459:313-8 pubmed
    ..When expressed in J82 cells, DH/PH domain-containing forms of KIAA0380 induced actin stress fibers, whereas expression of the RGS homology domain prevented lysophosphatidic acid (LPA)-induced stress fiber formation. ..
  3. Longhurst D, Watanabe M, Rothstein J, Jackson M. Interaction of PDZRhoGEF with microtubule-associated protein 1 light chains: link between microtubules, actin cytoskeleton, and neuronal polarity. J Biol Chem. 2006;281:12030-40 pubmed
    ..This coordinated action of the actin and microtubular cytoskeletons is essential for the development and maintenance of neuronal polarity. ..
  4. Yamada T, Ohoka Y, Kogo M, Inagaki S. Physical and functional interactions of the lysophosphatidic acid receptors with PDZ domain-containing Rho guanine nucleotide exchange factors (RhoGEFs). J Biol Chem. 2005;280:19358-63 pubmed
    ..Taken together, these results indicate that formation of the LPA receptor/PDZ domain-containing RhoGEF complex plays a pivotal role in LPA-induced RhoA activation. ..
  5. Suzuki N, Nakamura S, Mano H, Kozasa T. Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci U S A. 2003;100:733-8 pubmed
    ..These results demonstrate the biochemical mechanism of Rho activation through Galpha12 and that the regulation of RhoGEFs by heterotrimeric G proteins G1213 is further modulated by tyrosine phosphorylation. ..
  6. Driessens M, Olivo C, Nagata K, Inagaki M, Collard J. B plexins activate Rho through PDZ-RhoGEF. FEBS Lett. 2002;529:168-72 pubmed
    ..Our results demonstrate a role for PDZ-RhoGEF in B plexin-mediated activation of Rho/Rho kinase signaling, implicated in the regulation of axon guidance and cell migration. ..
  7. Perrot V, Vazquez Prado J, Gutkind J. Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF. J Biol Chem. 2002;277:43115-20 pubmed
    ..The association of Plexins with LARG and PDZ-RhoGEF thus provides a direct molecular mechanism by which semaphorins acting on Plexin B can control Rho, thereby regulating the actin-cytoskeleton during axonal guidance and cell migration. ..
  8. Swiercz J, Kuner R, Behrens J, Offermanns S. Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. Neuron. 2002;35:51-63 pubmed
  9. Banerjee J, Wedegaertner P. Identification of a novel sequence in PDZ-RhoGEF that mediates interaction with the actin cytoskeleton. Mol Biol Cell. 2004;15:1760-75 pubmed
    ..These results identify interaction with the actin cytoskeleton as a novel function for PDZ-RhoGEF, thus implicating actin interaction in organizing PDZ-RhoGEF signaling. ..

More Information


  1. Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind J. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem. 1999;274:5868-79 pubmed
  2. Longenecker K, Lewis M, Chikumi H, Gutkind J, Derewenda Z. Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases. Structure. 2001;9:559-69 pubmed
    ..Finally, we conclude that the strategy used to produce crystals was beneficial and might be applicable to other proteins resistant to crystallization. ..
  3. Derewenda U, Oleksy A, Stevenson A, Korczynska J, Dauter Z, Somlyo A, et al. The crystal structure of RhoA in complex with the DH/PH fragment of PDZRhoGEF, an activator of the Ca(2+) sensitization pathway in smooth muscle. Structure. 2004;12:1955-65 pubmed
    ..The DH domain makes several specific interactions with RhoA residues not conserved among other Rho family members, suggesting the molecular basis for the observed specificity. ..
  4. Cervantes Villagrana R, Adame García S, García Jiménez I, Color Aparicio V, Beltrán Navarro Y, König G, et al. Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. J Biol Chem. 2019;294:531-546 pubmed publisher
    ..We conclude that a coordinated mechanism prioritizes Gαq- and Gα13-mediated signaling to Rho over a Gβγ-dependent Rac pathway, attributed to heterotrimeric Gi proteins. ..
  5. Lee S, Cieply B, Yang Y, Peart N, Glaser C, Chan P, et al. Esrp1-Regulated Splicing of Arhgef11 Isoforms Is Required for Epithelial Tight Junction Integrity. Cell Rep. 2018;25:2417-2430.e5 pubmed publisher
    ..epithelial tight junction (TJ) integrity through loss of the epithelial isoform of Rho GTP exchange factor Arhgef11. Arhgef11 is required for the maintenance of TJs via RhoA activation and myosin light chain (MLC) phosphorylation...
  6. Wang T, Li B, Yuan X, Cui L, Wang Z, Zhang Y, et al. MiR-20a Plays a Key Regulatory Role in the Repair of Spinal Cord Dorsal Column Lesion via PDZ-RhoGEF/RhoA/GAP43 Axis in Rat. Cell Mol Neurobiol. 2019;39:87-98 pubmed publisher
    ..Thus, targeting the miR-20a/PDZ-RhoGEF /RhoA/GAP43 axis served as a novel strategy in promoting the sensory function recovery post-SCI. ..
  7. Murayama K, Kato Murayama M, Akasaka R, Terada T, Yokoyama S, Shirouzu M. Structure of the Rho-specific guanine nucleotide-exchange factor Xpln. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68:1455-9 pubmed publisher
    ..The crystal structure indicated that the α4-α5 loop in the DH domain is flexible and that the DH and PH domains interact with each other intramolecularly, thus suggesting that PH-domain rearrangement occurs upon RhoA binding. ..
  8. Chen Z, Medina F, Liu M, THOMAS C, Sprang S, Sternweis P. Activated RhoA binds to the pleckstrin homology (PH) domain of PDZ-RhoGEF, a potential site for autoregulation. J Biol Chem. 2010;285:21070-81 pubmed publisher
    ..PH bound to both forms of RhoA can be isolated by size-exclusion chromatography. This novel interaction between activated RhoA and PH could play a key role in regulation of RhoGEF activity in vivo. ..
  9. Cervantes Villagrana R, Color Aparicio V, Reyes Cruz G, Vazquez Prado J. Protumoral bone marrow-derived cells migrate via Gβγ-dependent signaling pathways and exhibit a complex repertoire of RhoGEFs. J Cell Commun Signal. 2019;: pubmed publisher
  10. Bagnato A, Rosanò L. Endothelin-1 receptor drives invadopodia: Exploiting how β-arrestin-1 guides the way. Small Gtpases. 2018;9:394-398 pubmed publisher
    ..Here, we summarize this novel activation of the RhoC pathway from ETAR/β-arr1 signaling that may be exploited therapeutically and discuss new perspectives for future directions of investigations. ..
  11. Yan J, Su R, Ao D, Wang Y, Wang H, Yang H. Genetic variants and clinical relevance associated with gestational diabetes mellitus in Chinese women: a case-control study. J Matern Fetal Neonatal Med. 2018;31:2115-2121 pubmed publisher
    ..Among these SNPs, we report for the first time that rs945508 in ARHGEF11, rs10804591 in PLXND1 and rs10245353 in NFE2L3 were associated with GDM.
  12. Chen C, Lee A, Liao C, Liu Y, Pan C. RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly. Proc Natl Acad Sci U S A. 2014;111:16568-73 pubmed publisher
    ..Our data represent a neuronal remodeling paradigm during development that reshapes the neural circuit by the coordinated removal of the dysfunctional synaptic branch compartment and compensatory extension of the primary neurite. ..
  13. Ding Z, Dhruv H, Kwiatkowska Piwowarczyk A, Ruggieri R, Kloss J, Symons M, et al. PDZ-RhoGEF Is a Signaling Effector for TROY-Induced Glioblastoma Cell Invasion and Survival. Neoplasia. 2018;20:1045-1058 pubmed publisher
    ..Taken together, these data suggest that PDZ-RhoGEF plays an important role in TROY signaling and provides insights into a potential node of vulnerability to limit GBM cell invasion and decrease therapeutic resistance. ..
  14. Sai X, Yonemura S, Ladher R. Junctionally restricted RhoA activity is necessary for apical constriction during phase 2 inner ear placode invagination. Dev Biol. 2014;394:206-16 pubmed publisher
    ..Apically polarized Celsr1 orients and recruits the Rho Guanine exchange factor (GEF) ArhGEF11 to apical junctions, thus restricting RhoA activity to the junctional membrane where it activates the Rho kinase ..
  15. D Amato L, Dell aversana C, Conte M, Ciotta A, Scisciola L, Carissimo A, et al. ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias. Epigenetics. 2015;10:6-18 pubmed publisher
    ..The finding that GEF protein modulation by HDAC inhibition impacts on cell differentiation may be important for understanding the antitumor mechanism(s) by which HDACi treatment stimulates differentiation in cancer. ..
  16. Zhang W, Su R, Lin L, Yang H. ARHGEF11 affecting the placental insulin signaling pathway in fetal macrosomia of normal glucose tolerance pregnant women. Placenta. 2018;63:7-14 pubmed publisher
    ..This study aimed to investigate the mechanism of Rho guanine nucleotide exchange factor 11 (ARHGEF11) and the insulin signaling pathway in placenta affecting fetal overgrowth in NGT and ..
  17. Mizuki Y, Takaki M, Sakamoto S, Okamoto S, Kishimoto M, Okahisa Y, et al. Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis. Int J Mol Sci. 2016;18: pubmed publisher
    ..b>Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical ..
  18. Yan Z, Ma S, Zhang Y, Ma L, Wang F, Li J, et al. The structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47. Biotechnol Lett. 2017;39:745-750 pubmed publisher
    ..3 Å structure of the RhoA-PDZRhoGEF-inhibitor HL47 ternary complex. This structure provides a new template for target-based pharmaceutical design against RhoA. ..
  19. Jia Z, Johnson A, Wang X, Guo Z, Dreisbach A, Lewin J, et al. Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial-Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat. PLoS ONE. 2015;10:e0132553 pubmed publisher
    Previously, genetic analyses identified that variants in Arhgef11 may influence kidney injury in the Dahl salt-sensitive (S) rat, a model of hypertensive chronic kidney disease...
  20. Hernández García R, Iruela Arispe M, Reyes Cruz G, Vázquez Prado J. Endothelial RhoGEFs: A systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells. Vascul Pharmacol. 2015;74:60-72 pubmed publisher
    ..we found that the most abundant endothelial RhoGEFs were: Tuba, FGD5, Farp1, ARHGEF17, TRIO, P-Rex1, ARHGEF15, ARHGEF11, ABR, Farp2, ARHGEF40, ALS, DOCK1, DOCK7 and DOCK6...
  21. Fine N, Dimitriou I, Rullo J, Sandi M, Petri B, Haitsma J, et al. GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation. J Cell Biol. 2016;215:107-119 pubmed
    ..Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection. ..
  22. Fonseca A, Carvalho E, Eriksson J, Pereira M. Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018;445:157-168 pubmed publisher
    ..Investigation of genes potentially involved in GLUT4 trafficking showed only a small effect on ARHGEF11 gene expression (p < 0.05)...
  23. Behuliak M, Vavřínová A, Bencze M, Polgárová K, Ergang P, Kuneš J, et al. Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens. 2015;33:2443-54 pubmed publisher
    ..mRNA expression of selected Rho-GEFs (Arhgef1, Arhgef11 and Arhgef12) was decreased only in adult SHR, whereas p63RhoGEF and CPI-17 expression was reduced in both age ..
  24. Scherer S, Cain M, Kanai S, Kaltenbronn K, Blumer K. Regulation of neurite morphogenesis by interaction between R7 regulator of G protein signaling complexes and G protein subunit G?13. J Biol Chem. 2017;292:9906-9918 pubmed publisher
    ..This mechanism expands the diversity of functions whereby R7-RGS complexes regulate critical aspects of nervous system development and function. ..
  25. Valon L, Marín Llauradó A, Wyatt T, Charras G, Trepat X. Optogenetic control of cellular forces and mechanotransduction. Nat Commun. 2017;8:14396 pubmed publisher
    ..We fused the catalytic domain (DHPH domain) of the RhoA activator ARHGEF11 to CRY2-mCherry (optoGEF-RhoA) and engineered its binding partner CIBN to bind either to the plasma membrane or ..
  26. Singh N, Janjanam J, Rao G. p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation. J Biol Chem. 2017;292:14080-14091 pubmed publisher
    ..We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs)...
  27. Chang Y, Pownall S, Jensen T, Mouaaz S, Foltz W, Zhou L, et al. The Rho-guanine nucleotide exchange factor PDZ-RhoGEF governs susceptibility to diet-induced obesity and type 2 diabetes. elife. 2015;4: pubmed publisher the mouse, we discovered a function for a RhoA-specific guanine nucleotide exchange factor PDZ-RhoGEF (Arhgef11) in white adipose tissue biology...
  28. Chang Y, Zhou L, Binari R, Manoukian A, Mak T, McNeill H, et al. The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila. PLoS ONE. 2016;11:e0152259 pubmed publisher
    ..Overexpression of DRhoGEF2, and it's functional mammalian ortholog PDZ-RhoGEF (ArhGEF11), at various stages of eye development, resulted in both dPKB/Akt-dependent and -independent phenotypes, ..
  29. Okuhira K, Fitzgerald M, Tamehiro N, Ohoka N, Suzuki K, Sawada J, et al. Binding of PDZ-RhoGEF to ATP-binding cassette transporter A1 (ABCA1) induces cholesterol efflux through RhoA activation and prevention of transporter degradation. J Biol Chem. 2010;285:16369-77 pubmed publisher
    ..Taken together, our results have identified a novel physical and functional interaction between ABCA1 and PDZ-RhoGEF/LARG, which activates RhoA, resulting in ABCA1 stabilization and cholesterol efflux activity...
  30. Yang J, Wu C, Stefănescu I, Jakobsson L, Chervoneva I, Horowitz A. RhoA inhibits neural differentiation in murine stem cells through multiple mechanisms. Sci Signal. 2016;9:ra76 pubmed publisher
    ..These results suggested that, in addition to inhibiting Noggin transcription, RhoA activity in wild-type murine embryonic stem cells also prevented neural differentiation by limiting Noggin secretion. ..
  31. Semprucci E, Tocci P, Cianfrocca R, Sestito R, Caprara V, Veglione M, et al. Endothelin A receptor drives invadopodia function and cell motility through the β-arrestin/PDZ-RhoGEF pathway in ovarian carcinoma. Oncogene. 2016;35:3432-42 pubmed publisher
  32. Bottcher Y, Schleinitz D, Tonjes A, Bluher M, Stumvoll M, Kovacs P. R1467H variant in the rho guanine nucleotide exchange factor 11 (ARHGEF11) is associated with impaired glucose tolerance and type 2 diabetes in German Caucasians. J Hum Genet. 2008;53:365-7 pubmed publisher
    The human rho guanine nucleotide exchange factor 11 (ARHGEF11) functions as an activator of rho GTPases and is supposed to influence insulin signalling...
  33. Ma L, Hanson R, Que L, Cali A, Fu M, Mack J, et al. Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians. Diabetes. 2007;56:1454-9 pubmed
    ..ARHGEF11, which encodes the Rho guanine nucleotide exchange factor 11, was analyzed as a positional candidate gene for this linkage because this protein may stimulate ..
  34. Spellmon N, Holcomb J, Niu A, Choudhary V, Sun X, Zhang Y, et al. Structural basis of PDZ-mediated chemokine receptor CXCR2 scaffolding by guanine nucleotide exchange factor PDZ-RhoGEF. Biochem Biophys Res Commun. 2017;485:529-534 pubmed publisher
  35. Zaritsky A, Tseng Y, Rabadán M, Krishna S, Overholtzer M, Danuser G, et al. Diverse roles of guanine nucleotide exchange factors in regulating collective cell migration. J Cell Biol. 2017;216:1543-1556 pubmed publisher
    ..Phenotype-based clustering of knockdown behaviors identified RHOA-ARHGEF18 and ARHGEF3-ARHGEF28-ARHGEF11 clusters, indicating that the latter may signal through other RHO-family GTPases...
  36. Jackson M, Song W, Liu M, Jin L, Dykes Hoberg M, Lin C, et al. Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature. 2001;410:89-93 pubmed
    ..Here we report the identification and characterization of two proteins, GTRAP41 and GTRAP48 (for glutamate transporter EAAT4 associated protein) that specifically interact with the intracellular carboxy-..
  37. Carter A, Gutowski S, Sternweis P. Regulated localization is sufficient for hormonal control of regulator of G protein signaling homology Rho guanine nucleotide exchange factors (RH-RhoGEFs). J Biol Chem. 2014;289:19737-46 pubmed publisher
    ..Thus, RH domains act as independent detectors for activated G?13 and are sufficient to modulate the activity of RhoGEFs by hormones via mediating their localization to substrate, membrane-associated RhoA. ..
  38. Nishimura T, Honda H, Takeichi M. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell. 2012;149:1084-97 pubmed publisher
    ..Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate...
  39. Dong N, Liu L, Shao F. A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. EMBO J. 2010;29:1363-76 pubmed publisher
    ..EspH represents the first example of targeting RhoGEFs by bacterial effectors, and our results also reveal an unprecedented mechanism used by enteric pathogens to counteract the host defence system. ..
  40. Itoh M, Radisky D, Hashiguchi M, Sugimoto H. The exon 38-containing ARHGEF11 splice isoform is differentially expressed and is required for migration and growth in invasive breast cancer cells. Oncotarget. 2017;8:92157-92170 pubmed publisher
    ..b>ARHGEF11 is a RhoGEF that was previously shown to bind to the tight junction protein ZO-1 at perijunctional actomyosin ..
  41. Fu M, Sabra M, Damcott C, Pollin T, Ma L, Ott S, et al. Evidence that Rho guanine nucleotide exchange factor 11 (ARHGEF11) on 1q21 is a type 2 diabetes susceptibility gene in the Old Order Amish. Diabetes. 2007;56:1363-8 pubmed
    b>Rho guanine nucleotide exchange factor 11 (ARHGEF11), located on chromosome 1q21, is involved in G protein signaling and is a pathway known to play a role in both insulin secretion and action...
  42. Okuhira K, Fitzgerald M, Sarracino D, Manning J, Bell S, Goss J, et al. Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux. J Biol Chem. 2005;280:39653-64 pubmed
    ..The approach used to identify beta1-syntrophin as an ABCA1-binding protein should prove useful in elucidating other protein interactions upon which ABCA1 function depends...
  43. Ito S, Okuda S, Abe M, Fujimoto M, Onuki T, Nishimura T, et al. Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells. Nat Commun. 2017;8:1834 pubmed publisher
    ..Thus, advanced carcinoma cells require elevated RhoA activity for establishing robust junctions, which triggers tension-sensitive reorganization of actin/adhesion regulators. ..
  44. Davidkova G, McCullumsmith R, Meador Woodruff J. Expression of ARHGEF11 mRNA in schizophrenic thalamus. Ann N Y Acad Sci. 2003;1003:375-7 pubmed
  45. Wang Q, Liu M, Kozasa T, Rothstein J, Sternweis P, Neubig R. Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells. J Biol Chem. 2004;279:28831-4 pubmed
    ..Suppression of p115rhoGEF had no effect. Thus different rhoGEFs (LARG and PDZrhoGEF) mediate downstream rho signaling by the thrombin and LPA receptors. ..
  46. Nicholas N, Pipili A, Lesjak M, Ameer Beg S, Geh J, Healy C, et al. PAK4 suppresses PDZ-RhoGEF activity to drive invadopodia maturation in melanoma cells. Oncotarget. 2016;7:70881-70897 pubmed publisher
    ..Our work points to an essential role for both PAKs during melanoma invasion but provides a significant advance in our understanding of differential PAK function. ..
  47. Liu J, Chen X, Guo Q, Ma X, Zhang J, Huang X, et al. Association of ARHGEF11 R1467H polymorphism with risk for type 2 diabetes mellitus and insulin resistance in Chinese population. Mol Biol Rep. 2011;38:2499-505 pubmed publisher
    The human Rho guanine nucleotide exchange factor 11 (ARHGEF11), located on chromosome 1q21, is an activator of Rho GTPases involved in G protein signaling pathway known to regulate insulin secretion and action...
  48. Banerjee J, Fischer C, Wedegaertner P. The amino acid motif L/IIxxFE defines a novel actin-binding sequence in PDZ-RhoGEF. Biochemistry. 2009;48:8032-43 pubmed publisher
    ..PDZ-RhoGEF exists in cells as a dimer, raising the possibility that PDZ-RhoGEF could influence actin structure in a manner independent of its ability to activate RhoA. ..
  49. Pascoe H, Gutowski S, Chen H, Brautigam C, Chen Z, Sternweis P, et al. Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF. Proc Natl Acad Sci U S A. 2015;112:14852-7 pubmed publisher
    ..Formation of secondary interfaces may be a general mechanism for increasing affinity and specificity of modular domain-mediated interactions. ..
  50. Gu J, Wu X, Dong Q, Romeo M, Lin X, Gutkind J, et al. A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans. Cancer. 2006;106:2716-24 pubmed
    ..The results suggest that there are interactions between RGS2, RGS6, and PDZ-RhoGEF and validate this family of proteins as key regulators of tumorigenesis. ..
  51. Jaiswal M, Gremer L, Dvorsky R, Haeusler L, Cirstea I, Uhlenbrock K, et al. Mechanistic insights into specificity, activity, and regulatory elements of the regulator of G-protein signaling (RGS)-containing Rho-specific guanine nucleotide exchange factors (GEFs) p115, PDZ-RhoGEF (PRG), and leukemia-associated RhoGEF (LARG). J Biol Chem. 2011;286:18202-12 pubmed publisher
  52. Zheng M, Cierpicki T, Momotani K, Artamonov M, Derewenda U, Bushweller J, et al. On the mechanism of autoinhibition of the RhoA-specific nucleotide exchange factor PDZRhoGEF. BMC Struct Biol. 2009;9:36 pubmed publisher
    ..The activation mechanism is likely to involve two independent steps, i.e. displacement of the RGSL domain and conformational change involving the autoinhibitory sequence motif containing several negatively charged residues. ..
  53. Akiyama K, Narita A, Nakaoka H, Cui T, Takahashi T, Yasuno K, et al. Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms. J Hum Genet. 2010;55:656-61 pubmed publisher
    ..78 × 10(-5) for rs7781293 of TMEM195; P=4.93 × 10(-5) for rs7550260 of ARHGEF11; and P=3.63 × 10(-5) for rs9864101 of IQSEC1) with probabilities of being false positives <0...
  54. Ying Z, Giachini F, Tostes R, Webb R. PYK2/PDZ-RhoGEF links Ca2+ signaling to RhoA. Arterioscler Thromb Vasc Biol. 2009;29:1657-63 pubmed publisher
    ..PYK2 and PDZ-RhoGEF are necessary for angiotensin II-induced RhoA activation and for Ca(2+) signaling to RhoA. ..
  55. Fine N, Dimitriou I, Rottapel R. Go with the flow: GEF-H1 mediated shear stress mechanotransduction in neutrophils. Small Gtpases. 2017;:1-9 pubmed publisher
    ..In our recent work, we showed that GEF-H1, a RhoA specific guanine nucleotide exchange factor (GEF), is required to maintain neutrophil motility and migration in response to shear stress...
  56. Togashi H, Nagata K, Takagishi M, Saitoh N, Inagaki M. Functions of a rho-specific guanine nucleotide exchange factor in neurite retraction. Possible role of a proline-rich motif of KIAA0380 in localization. J Biol Chem. 2000;275:29570-8 pubmed
    ..These results suggest that KIAA0380 plays an important role in neurite retraction through Rho-dependent signaling. ..
  57. Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, et al. Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors. Biochem Biophys Res Commun. 2002;297:32-7 pubmed
    ..Immunocytochemical analysis showed that LARG was recruited to plasma membrane by plexin-B1. These results suggest that PDZ domain-containing RhoGEFs play a role in Sema4D-plexin-B1 mediating signal transduction. ..
  58. Bielnicki J, Shkumatov A, Derewenda U, Somlyo A, Svergun D, Derewenda Z. Insights into the molecular activation mechanism of the RhoA-specific guanine nucleotide exchange factor, PDZRhoGEF. J Biol Chem. 2011;286:35163-75 pubmed publisher
    ..The molten globule region and the activation box become less ordered in the PRG-RhoA complex and dissociate from the RhoA-binding site, which may constitute a critical step leading to PRG activation. ..
  59. Mizuki Y, Takaki M, Okahisa Y, Sakamoto S, Kodama M, Ujike H, et al. Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population. Hum Psychopharmacol. 2014;29:552-8 pubmed publisher
    The human Rho guanine nucleotide exchange factor 11 (ARHGEF11) gene is one of the candidate genes for type 2 diabetes mellitus (T2DM). ARHGEF11 is mapped to chromosome 1q21, which has susceptible risk loci for T2DM and schizophrenia...
  60. Jiang X, Lu X, McNamara G, Liu X, Cubedo E, Sarosiek K, et al. HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway. Blood. 2010;116:5217-27 pubmed publisher
    ..This mechanism may underlie the limited dissemination and better outcome of patients with HGAL-expressing DLBCL and cHL. ..
  61. Wong K, Van Keymeulen A, Bourne H. PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells. J Cell Biol. 2007;179:1141-8 pubmed
    ..We propose a cooperative reinforcing mechanism at the back of cells, in which PRG, RhoA, ROCK, myosin II, and actomyosin spatially cooperate to consolidate attractant-induced contractility and ensure robust cell polarity. ..
  62. Oinuma I, Katoh H, Harada A, Negishi M. Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells. J Biol Chem. 2003;278:25671-7 pubmed
    ..We propose that Rnd1 plays an important role in the regulation of Plexin-B1 signaling, leading to Rho activation during axon guidance and cell migration. ..
  63. Artamonov M, Momotani K, Stevenson A, Trentham D, Derewenda U, Derewenda Z, et al. Agonist-induced Ca2+ sensitization in smooth muscle: redundancy of Rho guanine nucleotide exchange factors (RhoGEFs) and response kinetics, a caged compound study. J Biol Chem. 2013;288:34030-40 pubmed publisher
  64. Guo X, Li Y, Peng K, Hu Y, Li C, Xia B, et al. Solution structures and backbone dynamics of arsenate reductase from Bacillus subtilis: reversible conformational switch associated with arsenate reduction. J Biol Chem. 2005;280:39601-8 pubmed publisher