RACGAP1

Summary

Gene Symbol: RACGAP1
Description: Rac GTPase activating protein 1
Alias: CYK4, HsCYK-4, ID-GAP, MgcRacGAP, rac GTPase-activating protein 1, male germ cell RacGap, protein CYK4 homolog
Species: human
Products:     RACGAP1

Top Publications

  1. White E, Glotzer M. Centralspindlin: at the heart of cytokinesis. Cytoskeleton (Hoboken). 2012;69:882-92 pubmed publisher
    ..Because of these diverse functions, centralspindlin lies at the heart of the cytokinetic mechanism. ..
  2. Kawashima T, Hirose K, Satoh T, Kaneko A, Ikeda Y, Kaziro Y, et al. MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells. Blood. 2000;96:2116-24 pubmed
    ..We also isolated a full-length human MgcRacGAP cDNA, which encodes an additional N-terminal polypeptide of 105 amino acid residues compared with the previously ..
  3. Hirose K, Kawashima T, Iwamoto I, Nosaka T, Kitamura T. MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody. J Biol Chem. 2001;276:5821-8 pubmed
    We have recently cloned a cDNA for a full-length form of MgcRacGAP. Here we show using anti-MgcRacGAP antibodies that, unlike other known GAPs for Rho family, MgcRacGAP localized to the nucleus in interphase, accumulated to the mitotic ..
  4. Mishima M, Kaitna S, Glotzer M. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev Cell. 2002;2:41-54 pubmed
    ..Biochemical studies indicate that this complex, named centralspindlin, is a heterotetramer. Centralspindlin, but not its individual components, strongly promotes microtubule bundling in vitro. ..
  5. Zhao W, Fang G. MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis. Proc Natl Acad Sci U S A. 2005;102:13158-63 pubmed
    ..b>MgcRacGAP, a GTPase-activating protein for RhoA, is required for cytokinesis, but the mechanism of its action remains ..
  6. Tonozuka Y, Minoshima Y, Bao Y, Moon Y, Tsubono Y, Hatori T, et al. A GTPase-activating protein binds STAT3 and is required for IL-6-induced STAT3 activation and for differentiation of a leukemic cell line. Blood. 2004;104:3550-7 pubmed
    We previously identified a guanosine triphosphatase (GTPase)-activating protein (GAP) male germ cell Rac GAP (MgcRacGAP) that enhanced interleukin-6 (IL-6)-induced macrophage differentiation of murine M1 leukemia cells...
  7. Oceguera Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, et al. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005;168:221-32 pubmed
    ..Overexpression of dominant-negative mutants of Ect2 and MgcRacGAP, a Rho GTPase guanine nucleotide exchange factor and GTPase activating protein, respectively, or depletion of ..
  8. Niiya F, Xie X, Lee K, Inoue H, Miki T. Inhibition of cyclin-dependent kinase 1 induces cytokinesis without chromosome segregation in an ECT2 and MgcRacGAP-dependent manner. J Biol Chem. 2005;280:36502-9 pubmed
    ..The small GTPase RhoA and its regulators ECT2 and MgcRacGAP have been implicated in furrow ingression in mammalian cells, but the signaling upstream of these molecules ..
  9. Wolfe B, Takaki T, Petronczki M, Glotzer M. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009;7:e1000110 pubmed publisher
    ..Collectively, our data reveal that formation of the HsCyk-4-Ect2 complex is subject to multiple layers of regulation to ensure that RhoA activation occurs between the segregated sister chromatids during anaphase. ..

More Information

Publications103 found, 100 shown here

  1. Bastos R, Peñate X, Bates M, Hammond D, Barr F. CYK4 inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways during cytokinesis. J Cell Biol. 2012;198:865-80 pubmed publisher
    ..We demonstrate that the MKlp1-CYK4 centralspindlin complex is a guanosine triphosphatase-activating protein (GAP) for Rac1 and not RhoA and that CYK4 ..
  2. Kitamura T, Kawashima T, Minoshima Y, Tonozuka Y, Hirose K, Nosaka T. Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation. Cell Struct Funct. 2001;26:645-51 pubmed
    ..From this screening, we obtained a full length cDNA encoding a mouse homologue of human MgcRacGAP. Overexpression of the anti-sense MgcRacGAP profoundly inhibited IL-6-induced macrophage-differentiation of M1 ..
  3. Burkard M, Maciejowski J, Rodriguez Bravo V, Repka M, Lowery D, Clauser K, et al. Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells. PLoS Biol. 2009;7:e1000111 pubmed publisher
    ..we found that Plk1 binds and directly phosphorylates the HsCYK-4 subunit of centralspindlin (also known as MgcRacGAP) at the midzone...
  4. Lekomtsev S, Su K, Pye V, Blight K, Sundaramoorthy S, Takaki T, et al. Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis. Nature. 2012;492:276-9 pubmed publisher
    ..We demonstrate that the C1?domain of the centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids...
  5. Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao Y, et al. Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell. 2003;4:549-60 pubmed
    ..Among these, Aurora B, RhoA, and the GAP MgcRacGAP have been implicated in cytokinesis, but their underlying mechanisms of action have remained unclear...
  6. Lee J, Kamijo K, Ohara N, Kitamura T, Miki T. MgcRacGAP regulates cortical activity through RhoA during cytokinesis. Exp Cell Res. 2004;293:275-82 pubmed
    ..Here we show that expression of a GTPase-activating protein (GAP)-deficient mutant (R386A) of the Rho regulator MgcRacGAP induces abnormal cortical activity during cytokinesis in U2OS cells...
  7. Ban R, Irino Y, Fukami K, Tanaka H. Human mitotic spindle-associated protein PRC1 inhibits MgcRacGAP activity toward Cdc42 during the metaphase. J Biol Chem. 2004;279:16394-402 pubmed
    ..Data show that the PRC1 bait bound to MgcRacGAP, which is a GTPase-activating protein (GAP) for the Rho family GTPases also involved in cytokinesis...
  8. Yüce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005;170:571-82 pubmed
    ..Depletion of the other centralspindlin component, CYK-4/MgcRacGAP, prevents cortical accumulation of RhoA, F-actin, and myosin...
  9. Seguin L, Liot C, Mzali R, Harada R, Siret A, Nepveu A, et al. CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes Ect2, MgcRacGAP, and MKLP1 in S phase. Mol Cell Biol. 2009;29:570-81 pubmed publisher
    ..the GDP/GTP cycle of Rho GTPases is regulated by the exchange factor Ect2 and the GTPase activating protein MgcRacGAP which associates with the kinesin MKLP1 in the centralspindlin complex...
  10. Wang S, Ooi L, Hui K. Upregulation of Rac GTPase-activating protein 1 is significantly associated with the early recurrence of human hepatocellular carcinoma. Clin Cancer Res. 2011;17:6040-51 pubmed publisher
    To assess the significance of Rac GTPase-activating protein 1 (RACGAP1) expression in identifying HBV-positive human hepatocellular carcinoma (HCC) patients who are at high risk for recurrent disease...
  11. Ratheesh A, Gomez G, Priya R, Verma S, Kovacs E, Jiang K, et al. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens. Nat Cell Biol. 2012;14:818-828 pubmed publisher
    ..Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens. ..
  12. Toure A, Dorseuil O, Morin L, Timmons P, Jegou B, Reibel L, et al. MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells. J Biol Chem. 1998;273:6019-23 pubmed
    ..A protein of the predicted size 58 kDa, which we call MgcRacGAP, was detected in human testis as well as in germ cell tumor extracts by immunoblotting with antibodies specific ..
  13. Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee J, et al. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006;17:43-55 pubmed
    ..ECT2 forms a complex with the GTPase-activating protein MgcRacGAP and the kinesinlike protein MKLP1 at the central spindle, and the localization of ECT2 at the central spindle ..
  14. Canman J, Lewellyn L, Laband K, Smerdon S, Desai A, Bowerman B, et al. Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis. Science. 2008;322:1543-6 pubmed publisher
    ..Thus, inactivation of Rac by centralspindlin functions in parallel with RhoA activation to drive contractile ring constriction during cytokinesis. ..
  15. Milde Langosch K, Karn T, Muller V, Witzel I, Rody A, Schmidt M, et al. Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. Breast Cancer Res Treat. 2013;137:57-67 pubmed publisher
    ..Therefore, we compared mRNA expression data of Ki67, TOP2A, and RacGAP1 using a pool of 562 Affymetrix U133A microarrays from breast cancer samples...
  16. Ke H, Ke R, Li S, Li B, Lu H, Wang X. Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression. J Neurooncol. 2013;113:327-32 pubmed publisher
    Recently, Rac GTPase-activating protein 1 (RACGAP1) has been shown to have a critical role in various tumors...
  17. Tsai Y, Tseng Y, Chen P, Lin M, Wu C, Huang M, et al. Protective effects of elafin against adult asthma. Allergy Asthma Proc. 2016;37:15-24 pubmed publisher
    ..Further studies of elafin as a potential therapy for asthma are warranted. ..
  18. Wang C, Saar V, Leung K, Chen L, Wong G. Human amyloid ? peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans. Neurobiol Dis. 2018;109:88-101 pubmed publisher
    ..Taken together, our C. elegans double transgenic model provides insight on the fundamental neurobiologic processes underlying human AD and recapitulates selected transcriptomic changes observed in human AD brains. ..
  19. Hass H, Vogel U, Scheurlen M, Jobst J. Gene-expression Analysis Identifies Specific Patterns of Dysregulated Molecular Pathways and Genetic Subgroups of Human Hepatocellular Carcinoma. Anticancer Res. 2016;36:5087-5095 pubmed
    ..g. Rac GTPase activating protein 1 (RACGAP1), Rab GTPase YPT1 homolog (RAB1), and ADP-ribosylation factor-like 2 (ARL2)] and ..
  20. Harada S, Sizzle E, Lin M, Gocke C. Detection of Chromosomal Translocation in Hematologic Malignancies by a Novel DNA-Based Looped Ligation Assay (LOLA). Clin Chem. 2017;63:1278-1287 pubmed publisher
    ..The assay also has the added benefit of permitting rapid mapping of the breakpoints. ..
  21. Xu Q, Duan H, Gan L, Liu X, Chen F, Shen X, et al. MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model. Mol Med Rep. 2017;16:4501-4510 pubmed publisher
    ..These studies may provide new potential therapeutic options and pave the way to use circulating miR?1291 as a clinical biomarker of endometrial fibrosis. ..
  22. Zhou J, Wang W, Xie Y, Zhao Y, Chen X, Xu W, et al. Proteomics-Based Identification and Analysis of Proteins Associated with Helicobacter pylori in Gastric Cancer. PLoS ONE. 2016;11:e0146521 pubmed publisher
    ..pylori-infected and cagA-overexpressing cells. These results provide new insights into the molecular pathogenesis and treatment targets for gastric cancer with H. pylori infection. ..
  23. Sirohi K, Swarup G. Defects in autophagy caused by glaucoma-associated mutations in optineurin. Exp Eye Res. 2016;144:54-63 pubmed publisher
    ..How impaired autophagy caused by optineurin mutants leads to apoptosis and cell death, is yet to be explored. ..
  24. Rodriguez Fernandez I, Dell Angelica E. Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster. PLoS ONE. 2015;10:e0143026 pubmed publisher
    ..These results provide genetic evidence for new functional links connecting the machinery for biogenesis of LROs with molecules implicated in autophagy and small GTPase regulation. ..
  25. Mani M, Lee U, Yoon N, Kim H, Ko M, Seol W, et al. Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling. Mol Biol Cell. 2016;27:334-48 pubmed publisher
    ..Ectopic expression of shRNA-resistant DRG2 rescued Tfn recycling in DRG2-depleted cells. Our results demonstrate that DRG2 is an endosomal protein and a key regulator of Rab5 deactivation and Tfn recycling. ..
  26. Hirata Y, Brems H, Suzuki M, Kanamori M, Okada M, Morita R, et al. Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1. J Biol Chem. 2016;291:3124-34 pubmed publisher
  27. Thole T, Lodrini M, Fabian J, Wuenschel J, Pfeil S, Hielscher T, et al. Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival. Cell Death Dis. 2017;8:e2635 pubmed publisher
    ..and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by ..
  28. Blagoev B, Kratchmarova I, Ong S, Nielsen M, Foster L, Mann M. A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nat Biotechnol. 2003;21:315-8 pubmed
    ..SILAC combined with modification-based affinity purification is a useful approach to detect specific and functional protein-protein interactions. ..
  29. von Stülpnagel C, Funke C, Haberl C, Hörtnagel K, Jüngling J, Weber Y, et al. SYNGAP1 Mutation in Focal and Generalized Epilepsy: A Literature Overview and A Case Report with Special Aspects of the EEG. Neuropediatrics. 2015;46:287-91 pubmed publisher
    ..Furthermore, our case provides further support for efficacy of VPA in patients with SYNGAP1 mutation-related epilepsy. ..
  30. Goreczny G, Wormer D, Turner C. A Simplified System for Evaluating Cell Mechanosensing and Durotaxis In Vitro. J Vis Exp. 2015;:e52949 pubmed publisher
    ..This assay is readily adaptable to other cell types and/or knockdown of other proteins of interests to explore their respective roles in mechanosignaling and durotaxis. ..
  31. Sahin S, Işik Gönül I, Cakir A, Seckin S, Uluoglu O. Clinicopathological Significance of the Proliferation Markers Ki67, RacGAP1, and Topoisomerase 2 Alpha in Breast Cancer. Int J Surg Pathol. 2016;24:607-13 pubmed publisher
    Objectives The aims of this study are to evaluate expressions of Ki67, RacGAP1 (MgcRacGAP) and topoisomerase 2 alpha (TOP2a), the markers related with cell proliferation that have been proposed to affect the prognosis in the literature ..
  32. Yoo S, Latifkar A, Cerione R, Antonyak M. Cool-associated Tyrosine-phosphorylated Protein 1 Is Required for the Anchorage-independent Growth of Cervical Carcinoma Cells by Binding Paxillin and Promoting AKT Activation. J Biol Chem. 2017;292:3947-3957 pubmed publisher
  33. Zhuravlev Y, Hirsch S, Jordan S, Dumont J, Shirasu Hiza M, Canman J. CYK-4 regulates Rac, but not Rho, during cytokinesis. Mol Biol Cell. 2017;28:1258-1270 pubmed publisher
    ..Instead, we found that the rescue of cytokinesis in CYK-4 mutants by Rac inactivation was Cdc42 dependent. Together our data suggest that CYK-4 GAP activity opposes Rac (and perhaps Cdc42) during cytokinesis. ..
  34. Katori S, Noguchi Katori Y, Itohara S, Iwasato T. Spinal RacGAP ?-Chimaerin Is Required to Establish the Midline Barrier for Proper Corticospinal Axon Guidance. J Neurosci. 2017;37:7682-7699 pubmed publisher
    ..We propose that ?-chimaerin protects the midline barrier by mediating cell-repulsive signaling in juxta-midline cells, which prevents these cells from invading the midline. ..
  35. Mao C, Wang X, Liu Y, Wang M, Yan B, Jiang Y, et al. A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53. Cancer Res. 2018;78:3484-3496 pubmed publisher
    ..b>Significance: A cytosolic lncRNA functions as a tumor suppressor by activating the p53 pathway. Cancer Res; 78(13); 3484-96. ©2018 AACR. ..
  36. Liu H, Li Z, Li L, Peng H, Zhang Z. EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression. Tumour Biol. 2015;36:8325-31 pubmed publisher
    ..These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression. ..
  37. Jie L, Owens E, Plante L, Fang Z, Rensing D, Moeller K, et al. RGS2 squelches vascular Gi/o and Gq signaling to modulate myogenic tone and promote uterine blood flow. Physiol Rep. 2016;4: pubmed publisher
    ..Mutations that decrease vascular RGS2 expression may be a predisposition to decreased uterine blood flow. Targeting G protein signaling therefore might improve uterine and uteroplacental underperfusion disorders. ..
  38. Thuault S, Comunale F, Hasna J, Fortier M, Planchon D, Elarouci N, et al. The RhoE/ROCK/ARHGAP25 signaling pathway controls cell invasion by inhibition of Rac activity. Mol Biol Cell. 2016;27:2653-61 pubmed publisher
    ..Our results indicate that the RhoE/ROCK/ARHGAP25 signaling pathway promotes ARMS invasive potential and identify these proteins as potential therapeutic targets for ARMS treatment. ..
  39. Lin S, Chiang M, Shih H, Hsu L, Yeh T, Huang Y, et al. Regulator of G protein signaling 2 (Rgs2) regulates neural crest development through Ppar?-Sox10 cascade. Biochim Biophys Acta Mol Cell Res. 2017;1864:463-474 pubmed publisher
    ..This study reveals a unique regulatory mechanism, the Rgs2-Ppar?-Sox10 signaling cascade, and defines a key molecular regulator, Rgs2, in neural crest development. ..
  40. Rotoli D, Morales M, Avila J, Maeso M, García M, Mobasheri A, et al. Commitment of Scaffold Proteins in the Onco-Biology of Human Colorectal Cancer and Liver Metastases after Oxaliplatin-Based Chemotherapy. Int J Mol Sci. 2017;18: pubmed publisher
    ..Tough further research needs to be done in order to improve these assessments. ..
  41. Ozdemir E, Jang H, Gursoy A, Keskin O, Li Z, Sacks D, et al. Unraveling the molecular mechanism of interactions of the Rho GTPases Cdc42 and Rac1 with the scaffolding protein IQGAP2. J Biol Chem. 2018;293:3685-3699 pubmed publisher
    ..Rac1 could bind only to the RasGAP site of apo-GRD2 and could not facilitate IQGAP2 dimerization. Our detailed mechanistic insights help decipher how Cdc42 can stimulate actin polymerization in metastasis. ..
  42. Campbell Valois F, Sachse M, Sansonetti P, Parsot C. Escape of Actively Secreting Shigella flexneri from ATG8/LC3-Positive Vacuoles Formed during Cell-To-Cell Spread Is Facilitated by IcsB and VirA. MBio. 2015;6:e02567-14 pubmed publisher
    ..Our report reconciles several findings and may have broad implications for our understanding of the specific targeting of bacterial pathogens by LC3. ..
  43. Litosch I. Decoding Gαq signaling. Life Sci. 2016;152:99-106 pubmed publisher
    ..A better understanding of allosteric modulation may therefore identify a wealth of new targets to regulate signal strength and behavior. ..
  44. Subramanian J, Nedivi E. Filling the (SR)GAP in Excitatory/Inhibitory Balance. Neuron. 2016;91:205-7 pubmed publisher
  45. Lau K, Ma F, Xia J, Chan Q, Ng C, To K. Activation of GPR30 stimulates GTP-binding of G?i1 protein to sustain activation of Erk1/2 in inhibition of prostate cancer cell growth and modulates metastatic properties. Exp Cell Res. 2017;350:199-209 pubmed publisher
    ..by G-1 interfered expression of cell cycle regulators and machinery elements to modulate PCa cell growth and the RACGAP1 interactome to control metastatic properties...
  46. Lupu D, Orozco L, Wang Y, Cullen J, Pellegrini M, Zeisel S. Altered methylation of specific DNA loci in the liver of Bhmt-null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci. FASEB J. 2017;31:2090-2103 pubmed publisher
    ..M., Pellegrini, M., Zeisel, S. H. Altered methylation of specific DNA loci in the liver of Bhmt-null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci. ..
  47. Oguchi M, Noguchi K, Fukuda M. TBC1D12 is a novel Rab11-binding protein that modulates neurite outgrowth of PC12 cells. PLoS ONE. 2017;12:e0174883 pubmed publisher
    ..These findings indicated that TBC1D12 is a novel Rab11-binding protein that modulates neurite outgrowth of PC12 cells. ..
  48. He S, Mansour M, Zimmerman M, Ki D, Layden H, Akahane K, et al. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain. elife. 2016;5: pubmed publisher
    ..Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation. ..
  49. Redolfi N, Galla L, Maset A, Murru L, Savoia E, Zamparo I, et al. Oligophrenin-1 regulates number, morphology and synaptic properties of adult-born inhibitory interneurons in the olfactory bulb. Hum Mol Genet. 2016;25:5198-5211 pubmed publisher
    ..Altogether, our data indicated that OPHN1 plays a key role in regulating the number, morphology and function of adult-born inhibitory interneurons and contributed to identify potential therapeutic targets. ..
  50. Schwarz N, Lane A, Jovanovic K, Parfitt D, Aguilà M, Thompson C, et al. Arl3 and RP2 regulate the trafficking of ciliary tip kinesins. Hum Mol Genet. 2017;26:2480-2492 pubmed publisher
    ..Collectively, our findings suggest that RP2 and Arl3 regulate the trafficking of specific kinesins to cilia tips and provide additional evidence that TRIDs could be clinically beneficial for patients with this retinal degeneration...
  51. Laviolette L, Mermoud J, Calvo I, Olson N, Boukhali M, Steinlein O, et al. Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein. Nat Commun. 2017;8:15866 pubmed publisher
    ..The functional interaction between FLCN and Rab7A appears conserved across species. Our work highlights a mechanism explaining, at least in part, the tumour suppressor function of FLCN. ..
  52. Codocedo J, Montecinos Oliva C, Inestrosa N. Wnt-related SynGAP1 is a neuroprotective factor of glutamatergic synapses against Aβ oligomers. Front Cell Neurosci. 2015;9:227 pubmed publisher
    ..Overall, our findings suggest that SynGAP1 is part of the signaling pathways induced by Wnt-5a. Therefore, possibility exists that SynGAP is involved in the synaptic protection against Aβ oligomers. ..
  53. Yoo C, Naramoto S, Sparks J, Khan B, Nakashima J, Fukuda H, et al. Deletion analysis of AGD1 reveals domains crucial for plasma membrane recruitment and function in root hair polarity. J Cell Sci. 2018;131: pubmed publisher
  54. Graziano B, Gong D, Anderson K, Pipathsouk A, Goldberg A, Weiner O. A module for Rac temporal signal integration revealed with optogenetics. J Cell Biol. 2017;216:2515-2531 pubmed publisher
    ..This circuit is masked by feedback and redundancy when chemoattractant is used as the input, highlighting the value of probing signaling networks at intermediate nodes to deconvolve complex signaling cascades. ..
  55. Yoo S, Cerione R, Antonyak M. The Arf-GAP and Protein Scaffold Cat1/Git1 as a Multifaceted Regulator of Cancer Progression. Small Gtpases. 2017;: pubmed publisher
  56. Oue N, Yamamoto Y, Oshima T, Asai R, Ishikawa A, Uraoka N, et al. Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer. Pathobiology. 2017;: pubmed publisher
    ..We previously showed that the IQ motif containing the GTPase-activating protein 3 gene (IQGAP3) is upregulated in spheroid body-forming gastric cancer (GC) cells compared with parental cells. We investigated IQGAP3 expression in GC...
  57. Zhang L, Chen Q, An W, Yang F, Maguire E, Chen D, et al. Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia. Arterioscler Thromb Vasc Biol. 2017;37:2182-2194 pubmed publisher
  58. Marandi S, De Keyser N, Saliez A, Maernoudt A, Sokal E, Stilmant C, et al. Insulin signal transduction in rat small intestine: role of MAP kinases in expression of mucosal hydrolases. Am J Physiol Gastrointest Liver Physiol. 2001;280:G229-40 pubmed
  59. Martinez D, Langlois d Estaintot B, Granier T, Tolchard J, Courrèges C, Prouzet Mauleon V, et al. Structural evidence of a phosphoinositide-binding site in the Rgd1-RhoGAP domain. Biochem J. 2017;474:3307-3319 pubmed publisher
    ..Solid-state NMR spectroscopy experiments confirm the membrane interaction of the Rgd1p-RhoGAP domain upon the addition of PtdIns(4,5)P2 and indicate a slight membrane destabilization in the presence of the two partners. ..
  60. Amado Azevedo J, Reinhard N, van Bezu J, de Menezes R, van Beusechem V, van Nieuw Amerongen G, et al. A CDC42-centered signaling unit is a dominant positive regulator of endothelial integrity. Sci Rep. 2017;7:10132 pubmed publisher
    ..In conclusion, using a siRNA-based screen, we identified new regulators of barrier function and found that Cdc42 is a dominant positive regulator of endothelial integrity. ..
  61. Kurokawa K, Suda Y, Nakano A. Sar1 localizes at the rims of COPII-coated membranes in vivo. J Cell Sci. 2016;129:3231-7 pubmed publisher
    ..These results suggested that the reversible membrane association of Sar1 GTPase leads to its localization being restricted to the rims of COPII-coated membranes in vivo. ..
  62. Nguyen H, Hinman M, Guo X, Sharma A, Arakawa H, Luo G, et al. Neurofibromatosis type 1 alternative splicing is a key regulator of Ras/ERK signaling and learning behaviors in mice. Hum Mol Genet. 2017;26:3797-3807 pubmed publisher
    ..Therefore, the regulated alternative splicing of Nf1 is an important mechanism for fine-tuning Ras/ERK signaling as well as learning and memory in mice. ..
  63. Cornelia Koeberle S, Tanaka S, Kuriu T, Iwasaki H, Koeberle A, Schulz A, et al. Developmental stage-dependent regulation of spine formation by calcium-calmodulin-dependent protein kinase II? and Rap1. Sci Rep. 2017;7:13409 pubmed publisher
    ..CaMKII? is already known to be essential in learning and memory, but our findings suggest that CaMKII? plays an important activity-dependent role in restricting spine density during postnatal development. ..
  64. Chornyy S, Parnis A, Shmoish M, Cassel D. High abundance of ArfGAP1 found in the mossy fibers in hilus of the dentate gyrus region of the mouse brain. PLoS ONE. 2017;12:e0189659 pubmed publisher
    ..Taken together, our data suggest that ArfGAP1 can be used as a specific marker of the dentate mossy fibers and as for visualization of cortical layers in immunohistochemical studies. ..
  65. Tapon N, Nagata K, Lamarche N, Hall A. A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways. EMBO J. 1998;17:1395-404 pubmed
    ..When overexpressed in fibroblasts, POSH is a strong inducer of apoptosis. We propose that POSH acts as a scaffold protein and contributes to Rac-induced signal transduction pathways leading to diverse gene transcriptional changes. ..
  66. Cote J, Vuori K. Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity. J Cell Sci. 2002;115:4901-13 pubmed
    ..Our studies therefore identify a novel protein domain that interacts with and activates GTPases and suggest the presence of an evolutionarily conserved DOCK180-related superfamily of exchange factors. ..
  67. Jin X, Pan Y, Wang L, Ma T, Zhang L, Tang A, et al. Fructose-1,6-bisphosphatase Inhibits ERK Activation and Bypasses Gemcitabine Resistance in Pancreatic Cancer by Blocking IQGAP1-MAPK Interaction. Cancer Res. 2017;77:4328-4341 pubmed publisher
    ..i>Cancer Res; 77(16); 4328-41. ©2017 AACR. ..
  68. Remenyi R, Roberts G, Zothner C, Merits A, Harris M. SNAP-tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy. Sci Rep. 2017;7:5682 pubmed publisher
  69. Song O, Queval C, Iantomasi R, Delorme V, Marion S, Veyron Churlet R, et al. ArfGAP1 restricts Mycobacterium tuberculosis entry by controlling the actin cytoskeleton. EMBO Rep. 2018;19:29-42 pubmed publisher
    ..Altogether, these results reveal how cortical actin plays the role of a barrier to prevent mycobacterial entry into epithelial cells and indicate a novel role for ArfGAP1 as a restriction factor of host-pathogen interactions. ..
  70. Awasthi Y, Chaudhary P, Vatsyayan R, Sharma A, Awasthi S, Sharma R. Physiological and pharmacological significance of glutathione-conjugate transport. J Toxicol Environ Health B Crit Rev. 2009;12:540-51 pubmed publisher
    ..Furthermore, recent studies suggesting a link between RLIP76 mediated GS-E transport and cell cycle signaling are presented...
  71. Neel N, Rossman K, Martin T, Hayes T, Yeh J, Der C. The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effector. Mol Cell Biol. 2012;32:1374-86 pubmed publisher
    ..Instead, disruption of the ATPase function of RalBP1 impaired invadopodium formation. Our results identify a novel RalB-mediated biochemical and signaling mechanism for invadopodium formation...
  72. Saputo S, Norman K, Murante T, Horton B, Diaz J, Didone L, et al. Complex Haploinsufficiency-Based Genetic Analysis of the NDR/Lats Kinase Cbk1 Provides Insight into Its Multiple Functions in Candida albicans. Genetics. 2016;203:1217-33 pubmed publisher
    ..We also provide evidence that Rgd3 is a GAP for Cdc42 and show that its localization and phosphorylation are dependent on Cbk1. ..
  73. Von Stetina S, Liang J, Marnellos G, Mango S. Temporal regulation of epithelium formation mediated by FoxA, MKLP1, MgcRacGAP, and PAR-6. Mol Biol Cell. 2017;28:2042-2065 pubmed publisher
    ..Accumulation of DLG-1 protein is delayed by ZEN-4, acting in concert with its binding partner CYK-4/MgcRacGAP. Our structure-function analysis suggests that nuclear and kinesin functions are dispensable, whereas binding to ..
  74. Druey K. Emerging Roles of Regulators of G Protein Signaling (RGS) Proteins in the Immune System. Adv Immunol. 2017;136:315-351 pubmed publisher
  75. Takata A, Otsuka M, Kishikawa T, Yamagami M, Ishibashi R, Sekiba K, et al. RASAL1 is a potent regulator of hepatic stellate cell activity and liver fibrosis. Oncotarget. 2017;8:64840-64852 pubmed publisher
    ..These data demonstrate that deregulated RASAL1 expression levels and the affected downstream intracellular signaling are central mediators of perpetuated HSC activation and fibrogenesis in the liver...
  76. Majumdar S, Acharya A, Prakash B. Structural plasticity mediates distinct GAP-dependent GTP hydrolysis mechanisms in Rab33 and Rab5. FEBS J. 2017;284:4358-4375 pubmed publisher
    ..Taken together with the mechanisms seen for Rab1, it is evident that the observed variations in Rab and their GAP partners allow structural plasticity, or in other words, the choice of different catalytic mechanisms. ..
  77. Roth Flach R, Guo C, Danai L, Yawe J, Gujja S, Edwards Y, et al. Endothelial Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Is Critical for Lymphatic Vascular Development and Function. Mol Cell Biol. 2016;36:1740-9 pubmed publisher
    ..Taken together, these results reveal that EC Map4k4 is critical for lymphatic vascular development by regulating EC quiescence and lymphatic EC fate...
  78. Mi S, Lin M, Brouwer Visser J, Heim J, SMOTKIN D, Hebert T, et al. RNA-seq Identification of RACGAP1 as a Metastatic Driver in Uterine Carcinosarcoma. Clin Cancer Res. 2016;22:4676-86 pubmed publisher
    ..Rac GTPase-activating protein 1 (RACGAP1) was identified to be highly upregulated in uterine carcinosarcoma...
  79. Walkup W, Mastro T, Schenker L, Vielmetter J, Hu R, Iancu A, et al. A model for regulation by SynGAP-?1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density. elife. 2016;5: pubmed publisher
    ..Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP. ..
  80. Gu X, Orozco J, Saxton R, Condon K, Liu G, Krawczyk P, et al. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science. 2017;358:813-818 pubmed publisher
    ..Methionine-induced activation of mTORC1 requires the SAM binding capacity of SAMTOR. Thus, SAMTOR is a SAM sensor that links methionine and one-carbon metabolism to mTORC1 signaling. ..
  81. Thurman R, Siraliev Perez E, Campbell S. RAS ubiquitylation modulates effector interactions. Small Gtpases. 2017;:1-6 pubmed publisher
    ..These findings, taken together, suggest that mUbRASmay promoteactivation of RAS through a GAP defect, and facilitate RAF association and MAPK signaling in a nucleotide independent manner...
  82. Laufs U, Adam O, Strehlow K, Wassmann S, Konkol C, Laufs K, et al. Down-regulation of Rac-1 GTPase by Estrogen. J Biol Chem. 2003;278:5956-62 pubmed
    ..Rac1 GTPase gene-transcription and activity is regulated by 17 beta-estradiol, which may be an important molecular mechanism contributing to the cardiovascular effects of estrogens. ..
  83. Zhao W, Seki A, Fang G. Cep55, a microtubule-bundling protein, associates with centralspindlin to control the midbody integrity and cell abscission during cytokinesis. Mol Biol Cell. 2006;17:3881-96 pubmed
    ..Cep55 directly binds to MKLP1 in vitro and associates with the MKLP1-MgcRacGAP centralspindlin complex in vivo...
  84. Mott H, Owen D. Structure and function of RLIP76 (RalBP1): an intersection point between Ras and Rho signalling. Biochem Soc Trans. 2014;42:52-8 pubmed publisher
    ..This domain arrangement allows the two domains to engage Rho family and Ral small G-proteins simultaneously at the membrane. This suggests that RLIP76 is a node for Rho and Ras family signalling. ..
  85. Cuellar J, Valpuesta J, Wittinghofer A, Sot B. Domain topology of human Rasal. Biol Chem. 2017;: pubmed publisher
    ..These results help to understand the role of the different domains in controlling the dual GAP activity of GAP1 family proteins. ..
  86. Saito K, Fujimura Kamada K, Hanamatsu H, Kato U, Umeda M, Kozminski K, et al. Transbilayer phospholipid flipping regulates Cdc42p signaling during polarized cell growth via Rga GTPase-activating proteins. Dev Cell. 2007;13:743-51 pubmed
    ..We propose that a redistribution of phospholipids to the inner leaflet of the plasma membrane triggers the dispersal of Cdc42p from the apical growth site, through activation of GAPs...
  87. Jaber N, Mohd Naim N, Wang Z, Deleon J, Kim S, Zhong H, et al. Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus. J Cell Sci. 2016;129:4424-4435 pubmed
    ..Taken together, these results demonstrate that Vps34 has a previously unknown role in regulating Rab7 activity and late endosomal trafficking. ..
  88. Antony A C, Alone P. Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation. Biochem Biophys Res Commun. 2017;486:1110-1115 pubmed publisher
  89. Miao L, Yin R, Wu J, Yang S, Lin W, Pan S. The SRGAP2 SNPs, their haplotypes and G?×?E interactions on serum lipid traits. Sci Rep. 2017;7:11626 pubmed publisher
    ..Their haplotypes can explain much more serum lipid variation than any single SNP alone, especially for serum TC, HDL-C and ApoA1 levels. ..
  90. Oscarsson T, Walther A, Lengeler K, Wendland J. An Arf-GAP promotes endocytosis and hyphal growth of Ashbya gossypii. FEMS Microbiol Lett. 2017;364: pubmed publisher
    ..Our results indicate that this ARF-GTPase module plays an important role for filamentous hyphal growth. ..
  91. Zou Y, Shao Z, Peng J, Li F, Gong D, Wang C, et al. Crystal structure of triple-BRCT-domain of ECT2 and insights into the binding characteristics to CYK-4. FEBS Lett. 2014;588:2911-20 pubmed publisher
  92. van Adrichem A, Wennerberg K. MgcRacGAP inhibition stimulates JAK-dependent STAT3 activity. FEBS Lett. 2015;589:3859-65 pubmed publisher
    Male germ cell Rac GTPase-activating protein (MgcRacGAP) is a core regulator of cytokinesis...