gtpase activating proteins


Summary: Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.

Top Publications

  1. Ha V, Bharti S, Inoue H, Vass W, Campa F, Nie Z, et al. ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion. J Biol Chem. 2008;283:14915-26 pubmed publisher
    ..In comparing ASAP1 and ASAP3, we also found that invadopodia are dispensable for the invasive behavior of cells derived from a mammary carcinoma. ..
  2. Funai K, Cartee G. Contraction-stimulated glucose transport in rat skeletal muscle is sustained despite reversal of increased PAS-phosphorylation of AS160 and TBC1D1. J Appl Physiol (1985). 2008;105:1788-95 pubmed publisher
  3. Kim T, Healy K, Der C, Sciaky N, Bang Y, Juliano R. Effects of structure of Rho GTPase-activating protein DLC-1 on cell morphology and migration. J Biol Chem. 2008;283:32762-70 pubmed publisher
    ..Conversely, the expression of the amino-terminal domain of DLC-1 acts as a dominant negative and profoundly inhibits cell migration by displacing endogenous DLC-1 from focal adhesions. ..
  4. Lundmark R, Doherty G, Howes M, Cortese K, Vallis Y, Parton R, et al. The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway. Curr Biol. 2008;18:1802-8 pubmed publisher
  5. Gremer L, Gilsbach B, Ahmadian M, Wittinghofer A. Fluoride complexes of oncogenic Ras mutants to study the Ras-RasGap interaction. Biol Chem. 2008;389:1163-71 pubmed publisher
    ..We show that beryllium fluoride complexes are less sensitive to structural changes and report on a state close to but different from the ground state of the GAP-stimulated GTPase reaction. ..
  6. Ishikura S, Klip A. Muscle cells engage Rab8A and myosin Vb in insulin-dependent GLUT4 translocation. Am J Physiol Cell Physiol. 2008;295:C1016-25 pubmed publisher
    ..These results support a model whereby AS160, Rab8A, and myosin Vb are required for insulin-induced GLUT4 translocation in muscle cells, potentially as part of a linear signaling cascade. ..
  7. Gonzalez E, McGraw T. Insulin-modulated Akt subcellular localization determines Akt isoform-specific signaling. Proc Natl Acad Sci U S A. 2009;106:7004-9 pubmed publisher
    ..Together, our findings reveal the stimulus-induced subcellular compartmentalization of Akt kinases as a mechanism contributing to specify Akt isoform functions...
  8. Varfolomeev E, Goncharov T, Fedorova A, Dynek J, Zobel K, Deshayes K, et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 2008;283:24295-9 pubmed publisher
    ..Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation. ..
  9. Patino Lopez G, Dong X, Ben Aissa K, Bernot K, Itoh T, Fukuda M, et al. Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation. J Biol Chem. 2008;283:18323-30 pubmed publisher
    ..TCR enrichment at the IS was impaired by Rab35-DN. Thus, EPI64C and Rab35 regulate a recycling pathway in T cells and contribute to IS formation, most likely by participating in TCR transport to the IS. ..

More Information


  1. Rivera Molina F, Novick P. A Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway. Proc Natl Acad Sci U S A. 2009;106:14408-13 pubmed publisher
    ..GEF cascades working in concert with counter-current GAP cascades could generate a programmed series of Rab conversions responsible for regulating the choreography of membrane traffic. ..
  2. Singhal S, Yadav S, Drake K, Singhal J, Awasthi S. Hsf-1 and POB1 induce drug sensitivity and apoptosis by inhibiting Ralbp1. J Biol Chem. 2008;283:19714-29 pubmed publisher
    ..These findings indicate a novel model for mutual regulation of Hsf-1 and Ralbp1 through Ralbp1-mediated sequestration of Hsf-1 in the cellular cytoskeleton and Hsf-1-mediated inhibition of the transport activity of membrane-bound Ralbp1...
  3. Anderson D, Gill J, Cinalli R, Nance J. Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-6 from cell contacts. Science. 2008;320:1771-4 pubmed publisher
    ..Thus, PAC-1 provides a dynamic molecular link between cell contacts and PAR proteins that polarizes embryos radially. ..
  4. Singhal S, Yadav S, Singhal J, Sahu M, Sehrawat A, Awasthi S. Diminished drug transport and augmented radiation sensitivity caused by loss of RLIP76. FEBS Lett. 2008;582:3408-14 pubmed publisher
    ..Loss of RLIP76 confers sensitivity to xenobiotics and radiation due to the loss of a common transport mechanism for glutathione-electrophile conjugates and xenobiotics. ..
  5. Stöckli J, Davey J, Hohnen Behrens C, Xu A, James D, Ramm G. Regulation of glucose transporter 4 translocation by the Rab guanosine triphosphatase-activating protein AS160/TBC1D4: role of phosphorylation and membrane association. Mol Endocrinol. 2008;22:2703-15 pubmed publisher
  6. Cho Y, Challa S, Moquin D, Genga R, Ray T, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112-23 pubmed publisher
    ..Our findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections. ..
  7. Warnke M, Wanigasekara E, Singhal S, Singhal J, Awasthi S, Armstrong D. The determination of glutathione-4-hydroxynonenal (GSHNE), E-4-hydroxynonenal (HNE), and E-1-hydroxynon-2-en-4-one (HNO) in mouse liver tissue by LC-ESI-MS. Anal Bioanal Chem. 2008;392:1325-33 pubmed publisher
    ..The HNE/HNO method involves isocratic elution due to instability issues. Higher levels of GSHNE, HNE, and HNO were found in the knock-out animals, due to the absence of the RLIP76 transport mechanism. ..
  8. Liao Y, Shih Y, Lo S. Mutations in the focal adhesion targeting region of deleted in liver cancer-1 attenuate their expression and function. Cancer Res. 2008;68:7718-22 pubmed publisher
    ..Our studies have shown that mutations in DLC-1 may lead to loss of function and contribute to the tumorigenesis, and have revealed an allosteric regulation site for its RhoGAP activity. ..
  9. Bustos R, Forget M, SETTLEMAN J, Hansen S. Coordination of Rho and Rac GTPase function via p190B RhoGAP. Curr Biol. 2008;18:1606-11 pubmed publisher
  10. Gaudet M, Hunter K, Pharoah P, Dunning A, Driver K, Lissowska J, et al. Genetic variation in SIPA1 in relation to breast cancer risk and survival after breast cancer diagnosis. Int J Cancer. 2009;124:1716-20 pubmed publisher
    ..02, 0.88-1.17; 0.90, 0.72-1.11; 1.04, 0.90-1.21, respectively). Our results do not support a relationship between SIPA1 polymorphisms and breast cancer risk or subsequent survival. ..
  11. Singhal S, Sehrawat A, Mehta A, Sahu M, Awasthi S. Functional reconstitution of RLIP76 catalyzing ATP-dependent transport of glutathione-conjugates. Int J Oncol. 2009;34:191-9 pubmed
    ..K562 RLIP76 revealed higher specific activity of ATPase and transport for recombinant purified RLIP76, indicating that additional factors present in recombinant purified RLIP76 can modulate its transport activity...
  12. Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, et al. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. 2009;324:384-7 pubmed publisher
    ..Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis. ..
  13. Singhal S, Yadav S, Roth C, Singhal J. RLIP76: A novel glutathione-conjugate and multi-drug transporter. Biochem Pharmacol. 2009;77:761-9 pubmed publisher
  14. Xu X, Zhao Q, Rodrigo Peiris T, Brkljacic J, He C, Muller S, et al. RanGAP1 is a continuous marker of the Arabidopsis cell division plane. Proc Natl Acad Sci U S A. 2008;105:18637-42 pubmed publisher
    ..We propose that Arabidopsis RanGAP, a continuous positive protein marker of the plant division plane, has a role in spatial signaling during plant cell division. ..
  15. Miller A, Bement W. Regulation of cytokinesis by Rho GTPase flux. Nat Cell Biol. 2009;11:71-7 pubmed publisher guanine nucleotide exchange factors (GEFs) initiates a particular event, and Rho inactivation by GTPase activating proteins (GAPs) terminates that event...
  16. Ueda S, Fujimoto S, Hiramoto K, Negishi M, Katoh H. Dock4 regulates dendritic development in hippocampal neurons. J Neurosci Res. 2008;86:3052-61 pubmed publisher
    ..Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. ..
  17. Li W, Zou W, Zhao D, Yan J, Zhu Z, Lu J, et al. C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5. Development. 2009;136:2445-55 pubmed publisher
  18. Guegan F, Tatin F, Leste Lasserre T, Drutel G, Genot E, Moreau V. p190B RhoGAP regulates endothelial-cell-associated proteolysis through MT1-MMP and MMP2. J Cell Sci. 2008;121:2054-61 pubmed publisher
    ..In addition, our data reveal an unsuspected role for p190B in the expression of the two collaborative proteases MT1-MMP and MMP2, thereby affecting matrix remodelling and angiogenesis. ..
  19. Drin G, Morello V, Casella J, Gounon P, Antonny B. Asymmetric tethering of flat and curved lipid membranes by a golgin. Science. 2008;320:670-3 pubmed publisher
    ..Because membrane curvature constantly changes during vesicular trafficking, this mode of tethering suggests a way to maintain the Golgi architecture without compromising membrane flow. ..
  20. Manu -, Surkova S, Spirov A, Gursky V, Janssens H, Kim A, et al. Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation. PLoS Biol. 2009;7:e1000049 pubmed publisher
    ..More generally, we show that the complex multigenic phenomenon of canalization can be understood at a quantitative and predictive level by the application of a precise dynamical model...
  21. Jedrychowski M, Gartner C, Gygi S, Zhou L, Herz J, Kandror K, et al. Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important vesicle component and target of insulin signaling. J Biol Chem. 2010;285:104-14 pubmed publisher
    ..Furthermore, adipose-specific LRP1 knock-out mice also exhibit decreased GLUT4 expression. These findings suggest LRP1 is an important component of GSVs, and its expression is needed for the formation of fully functional GSVs...
  22. Ko F, Yeung Y, Wong C, Chan L, Poon R, Ng I, et al. Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma. Liver Int. 2010;30:139-48 pubmed publisher
    ..DLC1alpha was underexpressed and clinically relevant in human HCCs. ..
  23. Frasa M, Maximiano F, Smolarczyk K, Francis R, Betson M, Lozano E, et al. Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation. Curr Biol. 2010;20:198-208 pubmed publisher
    ..Thus, the integration of Rac1 and Rab7 activities by Armus provides an important regulatory node for E-cadherin turnover and stability of cell-cell contacts. ..
  24. Kim T, Vigil D, Der C, Juliano R. Role of DLC-1, a tumor suppressor protein with RhoGAP activity, in regulation of the cytoskeleton and cell motility. Cancer Metastasis Rev. 2009;28:77-83 pubmed publisher
    ..We then delineate the characteristics of DLC-1 and other members of its family, and describe how they may have multiple effects on the regulation of cell polarity, actin organization, and cell migration. ..
  25. D Avino P, Takeda T, Capalbo L, Zhang W, Lilley K, Laue E, et al. Interaction between Anillin and RacGAP50C connects the actomyosin contractile ring with spindle microtubules at the cell division site. J Cell Sci. 2008;121:1151-8 pubmed publisher
    ..Thus, in addition to its role in activating RhoA signalling, RacGAP50C also controls the proper assembly of the actomyosin ring by interacting with Anillin at the cleavage furrow. ..
  26. Matsuda M, Kobayashi Y, Masuda S, Adachi M, Watanabe T, Yamashita J, et al. Identification of adherens junction-associated GTPase activating proteins by the fluorescence localization-based expression cloning. Exp Cell Res. 2008;314:939-49 pubmed publisher
    ..Furthermore, cDNAs for ARHGAP12 and SPAL3, two putative GTPase activating proteins (GAPs) for small G proteins, were cloned as novel components of the junctional complex...
  27. Tong Z, Gao X, Howell A, Bose I, Lew D, Bi E. Adjacent positioning of cellular structures enabled by a Cdc42 GTPase-activating protein-mediated zone of inhibition. J Cell Biol. 2007;179:1375-84 pubmed publisher
    ..Thus, Cdc42 activators and GAPs establish concentric zones of action such that polarization is directed to occur adjacent to but not within the previous cell division site. ..
  28. Levi S, Rawet M, Kliouchnikov L, Parnis A, Cassel D. Topology of amphipathic motifs mediating Golgi localization in ArfGAP1 and its splice isoforms. J Biol Chem. 2008;283:8564-72 pubmed publisher
  29. Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, et al. Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells. Blood. 2008;111:2973-6 pubmed publisher
    ..In contrast, DOCK2(-/-) mDCs did not show any defects in Rac activation and migration. These results indicate that pDCs and mDCs use distinct molecules to activate Rac during chemotaxis. ..
  30. Touré A, Mzali R, Liot C, Seguin L, Morin L, Crouin C, et al. Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase. FEBS Lett. 2008;582:1182-8 pubmed publisher
    ..Therefore, PP2A may regulate cytokinesis by dephosphorylating MgcRacGAP and its interacting partners. ..
  31. Chavez J, Roach W, Keller S, Lane W, Lienhard G. Inhibition of GLUT4 translocation by Tbc1d1, a Rab GTPase-activating protein abundant in skeletal muscle, is partially relieved by AMP-activated protein kinase activation. J Biol Chem. 2008;283:9187-95 pubmed publisher
    ..The above findings strongly suggest that Tbc1d1 is a component in the signal transduction pathway leading to AMPK-stimulated GLUT4 translocation in muscle. ..
  32. Taylor E, An D, Kramer H, Yu H, Fujii N, Roeckl K, et al. Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle. J Biol Chem. 2008;283:9787-96 pubmed publisher
    ..TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction. Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator. ..
  33. Cheung M, Xue Y, Zhou L, Li M, Sun S, Lam H. An ancient P-loop GTPase in rice is regulated by a higher plant-specific regulatory protein. J Biol Chem. 2010;285:37359-69 pubmed publisher
    ..This work suggests that during evolution, an ancestral P-loop GTPase/ATPase may acquire new regulation and function(s) by the evolution of a lineage-specific regulatory protein...
  34. Jennings M, Pavitt G. eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature. 2010;465:378-81 pubmed publisher
    ..Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls. ..
  35. Tang X, Jang S, Okada M, Chan C, Feng Y, Liu Y, et al. Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B. Nat Cell Biol. 2008;10:698-706 pubmed publisher
    ..Thus, PIKE-L acts as a downstream survival effector for netrin-1 through UNC5B in the nervous system. ..
  36. Seaman M, Harbour M, Tattersall D, Read E, Bright N. Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. J Cell Sci. 2009;122:2371-82 pubmed publisher
    ..We therefore propose that recruitment of the cargo-selective VPS35/29/26 complex is catalysed by Rab7 and inhibited by the Rab-GAP protein, TBC1D5. ..
  37. Katoh Y, Katoh M. Integrative genomic analyses on GLI1: positive regulation of GLI1 by Hedgehog-GLI, TGFbeta-Smads, and RTK-PI3K-AKT signals, and negative regulation of GLI1 by Notch-CSL-HES/HEY, and GPCR-Gs-PKA signals. Int J Oncol. 2009;35:187-92 pubmed
    ..Together these facts indicate that Hedgehog, TGFbeta, and RTK signals positively regulate GLI1, and that Notch, and GsPCR signals negatively regulate the GLI1. ..
  38. Dreyer H, Drummond M, Glynn E, Fujita S, Chinkes D, Volpi E, et al. Resistance exercise increases human skeletal muscle AS160/TBC1D4 phosphorylation in association with enhanced leg glucose uptake during postexercise recovery. J Appl Physiol (1985). 2008;105:1967-74 pubmed publisher
    ..05). We conclude that resistance exercise increases AS160/TBC1D4 phosphorylation in association with an increase in leg glucose uptake during postexercise recovery. ..
  39. Ye K. Phosphorylation of merlin regulates its stability and tumor suppressive activity. Cell Adh Migr. 2007;1:196-8 pubmed
  40. Kim J, Zeng C, Nayak T, Shao R, Huang A, Oakley B, et al. Timely septation requires SNAD-dependent spindle pole body localization of the septation initiation network components in the filamentous fungus Aspergillus nidulans. Mol Biol Cell. 2009;20:2874-84 pubmed publisher
    ..Therefore, we conclude that SPB localization of SIN components is not essential for septation per se, but critical for septation to take place in a timely manner in A. nidulans. ..
  41. Oguri M, Kato K, Yokoi K, Yoshida T, Watanabe S, Metoki N, et al. Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals. Am J Hypertens. 2010;23:70-7 pubmed publisher
    ..SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined. ..
  42. Yi S, Lee H, Groffen J, Heisterkamp N. Bcr/Abl P190 interaction with Spa-1, a GTPase activating protein for the small GTPase Rap1. Int J Mol Med. 2008;22:453-8 pubmed
    ..The binding of Bcr/Abl to Spa-1 may cause aberrant subcellular location of Spa-1 and affect migration of these cells. ..
  43. Cavet M, Pang J, Yin G, Berk B. An epidermal growth factor (EGF) -dependent interaction between GIT1 and sorting nexin 6 promotes degradation of the EGF receptor. FASEB J. 2008;22:3607-16 pubmed publisher
    ..Our findings suggest a new role for GIT1 in tyrosine kinase receptor trafficking. ..
  44. Gotoh K, Tanaka Y, Nishikimi A, Nakamura R, Yamada H, Maeda N, et al. Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. J Exp Med. 2010;207:721-30 pubmed publisher
    ..Owing to its hematopoietic cell-specific expression, DOCK2 may serve as a therapeutic target for type I IFN-related autoimmune diseases. ..
  45. 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
  46. Barresi V, Ragusa A, Fichera M, Musso N, Castiglia L, Rappazzo G, et al. Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome. BMC Med Genomics. 2010;3:28 pubmed publisher
    ..Moreover a novel alternative splicing transcript of such gene, predominantly expressed in brain tissues, was identified. ..
  47. Ohgushi M, Matsumura M, Eiraku M, Murakami K, Aramaki T, Nishiyama A, et al. Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells. Cell Stem Cell. 2010;7:225-39 pubmed publisher
    ..Thus, the Abr-dependent "Rho-high/Rac-low" state plays a decisive role in initiating the dissociation-induced actomyosin hyperactivation and apoptosis in hESCs. ..
  48. Shimizu A, Mammoto A, Italiano J, Pravda E, Dudley A, Ingber D, et al. ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells. J Biol Chem. 2008;283:27230-8 pubmed publisher
    ..Cells treated with p190RhoGAP small interfering RNA also did not inactivate RhoA. Together, these results suggested that ABL2/ARG is a novel mediator of SEMA3F-induced RhoA inactivation and collapsing activity. ..
  49. Bass M, Morgan M, Roach K, Settleman J, Goryachev A, Humphries M. p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4. J Cell Biol. 2008;181:1013-26 pubmed publisher
    ..This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion. ..
  50. Zhou X, Yang X, Popescu N. Synergistic antineoplastic effect of DLC1 tumor suppressor protein and histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), on prostate and liver cancer cells: perspectives for therapeutics. Int J Oncol. 2010;36:999-1005 pubmed
    ..Current in vitro results validate this protocol as a potentially new therapeutic option in certain cancers. ..
  51. Pagnamenta A, Bacchelli E, de Jonge M, Mirza G, Scerri T, Minopoli F, et al. Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia. Biol Psychiatry. 2010;68:320-8 pubmed publisher
  52. Coon B, Burgner J, Camonis J, Aguilar R. The epsin family of endocytic adaptors promotes fibrosarcoma migration and invasion. J Biol Chem. 2010;285:33073-81 pubmed publisher
    ..We propose that the observed up-regulation of both epsin and RalBP1 in certain cancers contributes to their invasive characteristics...
  53. Potet F, Petersen C, Boutaud O, Shuai W, Stepanovic S, Balser J, et al. Genetic screening in C. elegans identifies rho-GTPase activating protein 6 as novel HERG regulator. J Mol Cell Cardiol. 2009;46:257-67 pubmed publisher
    ..These data link a rhoGAP-activated PLC pathway to HERG membrane expression and implicate this family of proteins as candidate genes in disorders involving HERG. ..