Rap1a

Summary

Gene Symbol: Rap1a
Description: RAS-related protein 1a
Alias: AI848598, G-22K, Krev-1, Rap1, ras-related protein Rap-1A, GTP-binding protein SMG-P21A, ras-related protein Krev-1
Species: mouse
Products:     Rap1a

Top Publications

  1. Lee H, Gaughan J, Tsygankov A. c-Cbl facilitates cytoskeletal effects in v-Abl transformed fibroblast through Rac1- and Rap1-mediated signaling. Int J Biochem Cell Biol. 2008;40:1930-43 pubmed publisher
    ..the individual contributions of small GTPases to these effects, we assessed the roles of endogenous Rac1, RhoA and Rap1 in the c-Cbl-dependent spreading and migration of v-Abl-transformed fibroblasts overexpressing c-Cbl, using RNAi...
  2. Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele J, Zwartkruis F. Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Mol Cell Biol. 2006;26:643-53 pubmed
    ..To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile...
  3. Birukova A, Fu P, Xing J, Birukov K. Rap1 mediates protective effects of iloprost against ventilator-induced lung injury. J Appl Physiol (1985). 2009;107:1900-10 pubmed publisher
    ..We tested a role of cAMP-activated Epac-Rap1 pathway in the barrier protective effects of PGI(2) analog iloprost in the murine model of ventilator-induced lung ..
  4. Severson E, Lee W, Capaldo C, Nusrat A, Parkos C. Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell. 2009;20:1916-25 pubmed publisher
    ..The functional effects observed were secondary to decreased levels of Rap1A because knockdown of Rap1A, but not Rap1B, resulted in decreased beta1 integrin levels and reduced cell migration...
  5. Lin K, Freeman S, Zabetian S, Brugger H, Weber M, Lei V, et al. The rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands. Immunity. 2008;28:75-87 pubmed publisher
    ..Thus by controlling B cell morphology and cytoskeletal organization, Rap might play a key role in the activation of B cells by particulate and cell-associated antigens. ..
  6. Li Y, Yan J, De P, Chang H, Yamauchi A, Christopherson K, et al. Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. J Immunol. 2007;179:8322-31 pubmed
    The Ras-related GTPases Rap1a and 1b have been implicated in multiple biological events including cell adhesion, free radical production, and cancer...
  7. Lakshmikanthan S, Sobczak M, Chun C, Henschel A, Dargatz J, Ramchandran R, et al. Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin ?v??. Blood. 2011;118:2015-26 pubmed publisher
    ..b>Rap1a and Rap1b, 2 highly homologous small G proteins, are both required for angiogenesis in vivo and for normal EC ..
  8. Stokman G, Qin Y, Genieser H, Schwede F, De Heer E, Bos J, et al. Epac-Rap signaling reduces cellular stress and ischemia-induced kidney failure. J Am Soc Nephrol. 2011;22:859-72 pubmed publisher
  9. Carmona G, Göttig S, Orlandi A, Scheele J, Bauerle T, Jugold M, et al. Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis. Blood. 2009;113:488-97 pubmed publisher
    ..Human umbilical vein endothelial cells (HUVECs) express Rap1a and Rap1b mRNA...

More Information

Publications84

  1. Franco S, Martinez Garay I, Gil Sanz C, Harkins Perry S, Muller U. Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex. Neuron. 2011;69:482-97 pubmed publisher
    ..During migration, Dab1 acts in translocating neurons to stabilize their leading processes in a Rap1-dependent manner. Rap1, in turn, controls cadherin function to regulate somal translocation...
  2. Menasche G, Kliche S, Chen E, Stradal T, Schraven B, Koretzky G. RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation. Mol Cell Biol. 2007;27:4070-81 pubmed
    ..adapter protein) and SKAP-55 (55-kDa src kinase-associated phosphoprotein) and the small GTPase Rap1. Herein, we provide evidence linking ADAP and SKAP-55 to RIAM, a recently described adapter protein that binds ..
  3. Yan J, Li F, Ingram D, Quilliam L. Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions. Mol Cell Biol. 2008;28:5803-10 pubmed publisher
    ..Blood vessel growth into fibroblast growth factor 2 (FGF2)-containing Matrigel plugs was absent from rap1a(-/-) mice, and aortic rings derived from rap1a(-/-) mice failed to sprout primitive tubes in response to FGF2, ..
  4. Abreu J, Krausz S, Dontje W, Grabiec A, de Launay D, Nolte M, et al. Sustained T cell Rap1 signaling is protective in the collagen-induced arthritis model of rheumatoid arthritis. Arthritis Rheum. 2010;62:3289-99 pubmed publisher
    Defective activation of T cell receptor-proximal signaling proteins, such as the small GTPase Rap1, is thought to contribute to the pathologic behavior of rheumatoid arthritis (RA) synovial T cells...
  5. Zemojtel T, Duchniewicz M, Zhang Z, Paluch T, Luz H, Penzkofer T, et al. Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity. BMC Evol Biol. 2010;10:55 pubmed publisher
    ..We identified two murine and one human-specific retrogene of Rap1A and Rap1B, which encode proteins that differ by only a few amino acids from their parental Rap1 proteins...
  6. Zieba B, Artamonov M, Jin L, Momotani K, Ho R, Franke A, et al. The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity. J Biol Chem. 2011;286:16681-92 pubmed publisher
    ..We report a new mechanism of cAMP-mediated relaxation through Epac, a GTP exchange factor for the small GTPase Rap1 resulting in an increase in Rap1 activity and suppression of RhoA activity...
  7. Ishihara S, Nishikimi A, Umemoto E, Miyasaka M, Saegusa M, Katagiri K. Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis. Nat Commun. 2015;6:8982 pubmed publisher
    b>Rap1-GTP activates leukocyte function-associated antigen-1 (LFA-1) to induce arrest on the high endothelial venule (HEV)...
  8. Kondoh N, Noda M, Fisher R, Schweinfest C, Papas T, Kondoh A, et al. The S29 ribosomal protein increases tumor suppressor activity of K rev-1 gene on v-K ras-transformed NIH3T3 cells. Biochim Biophys Acta. 1996;1313:41-6 pubmed
  9. Lin K, Tan P, Freeman S, Lam M, McNagny K, Gold M. The Rap GTPases regulate the migration, invasiveness and in vivo dissemination of B-cell lymphomas. Oncogene. 2010;29:608-15 pubmed publisher
    ..These findings suggest that Rap or its effectors could be novel targets for treating B-cell lymphomas. ..
  10. Katayama Y, Sekai M, Hattori M, Miyoshi I, Hamazaki Y, Minato N. Rap signaling is crucial for the competence of IL-7 response and the development of B-lineage cells. Blood. 2009;114:1768-75 pubmed publisher
    ..With the use of transgenic mice conditionally expressing a bona fide dominant-negative Rap1 mutant, Rap1A17, capable of inhibiting the activation of all Rap family members in B-lineage cells (mb...
  11. Wani M, Denko N, Stambrook P. Expression of Rap 1 suppresses genomic instability of H-ras transformed mouse fibroblasts. Somat Cell Mol Genet. 1997;23:123-33 pubmed
    ..Furthermore fluorescent-in-situ hybridization (FISH) with a pancentromeric mouse probe showed that elevated levels of chromosome aberrations in cells expressing H-ras were also suppressed after co-expression of Rap 1. ..
  12. Ueda Y, Kondo N, Ozawa M, Yasuda K, Tomiyama T, Kinashi T. Sema3e/Plexin D1 Modulates Immunological Synapse and Migration of Thymocytes by Rap1 Inhibition. J Immunol. 2016;196:3019-31 pubmed publisher
    ..class III semaphorin E (sema3e), a guidance molecule during neural and vascular development, directly inhibited Rap1 activation and LFA-1-dependent adhesion through the GTPase-activating protein activity of plexin D1...
  13. Li L, Kim J, Boussiotis V. Rap1A regulates generation of T regulatory cells via LFA-1-dependent and LFA-1-independent mechanisms. Cell Immunol. 2010;266:7-13 pubmed publisher
    The small GTPase Rap1A has a critical role in regulating cell-matrix and cell-cell adhesion. In T lymphocytes, Rap1A mediates LFA-1 activation and LFA-1-mediated adhesion...
  14. Ring S, Pushkarevskaya A, Schild H, Probst H, Jendrossek V, Wirsdörfer F, et al. Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway. J Immunol. 2015;194:3735-44 pubmed publisher
    ..in DC after contact to Treg revealed increased levels of cAMP, followed by activation of Epac1 and the GTPase Rap1. Subsequently activated Rap1 localized to the subcortical actin cytoskeleton in DC, providing a means by which ..
  15. Qiao S, Homayouni R. Dab2IP Regulates Neuronal Positioning, Rap1 Activity and Integrin Signaling in the Developing Cortex. Dev Neurosci. 2015;37:131-41 pubmed publisher
    ..Previously, we found that Dab2IP regulates multipolar transition in cortical neurons. Others have shown that Rap1 regulates the transition from multipolar to bipolar morphology in migrating postmitotic neurons through N-cadherin ..
  16. Wilson C, Parker L, Hall C, Smyczek T, Mak J, Crow A, et al. Rasip1 regulates vertebrate vascular endothelial junction stability through Epac1-Rap1 signaling. Blood. 2013;122:3678-90 pubmed publisher
    ..We also found that endogenous RASIP1 in ECs binds Ras-related protein 1 (RAP1), but not Ras homolog gene family member A or cell division control protein 42 homolog...
  17. Temeles G, Ram P, Rothstein J, Schultz R. Expression patterns of novel genes during mouse preimplantation embryogenesis. Mol Reprod Dev. 1994;37:121-9 pubmed
    ..The expression of the gene in Class 3 declined during oocyte maturation, but then showed a transient increase at the one-cell stage, with only a very slight increase in synthesis at either the eight-cell or blastocyst stage. ..
  18. Milani R, Ferreira C, Granjeiro J, Paredes Gamero E, Silva R, Justo G, et al. Phosphoproteome reveals an atlas of protein signaling networks during osteoblast adhesion. J Cell Biochem. 2010;109:957-66 pubmed publisher
    ..activated upon integrin activation, our results showed a novel network involving signaling proteins such as Rap1A, PKA, PKC, and GSK3beta during osteoblast adhesion on polystyrene...
  19. Hara S, Nakaseko C, Yamasaki S, Hattori M, Bos J, Saito Y, et al. Involvement of Rap-1 activation and early termination of immune synapse in CTLA-4-mediated negative signal. Hematology. 2009;14:150-8 pubmed publisher
    ..These results suggest that Rap-1 is activated upon CTLA-4 ligation and mediates inhibitory signals through prevention of IS formation. ..
  20. Chislock E, Pendergast A. Abl family kinases regulate endothelial barrier function in vitro and in mice. PLoS ONE. 2013;8:e85231 pubmed publisher
    ..we show that loss of Abl kinase activity was accompanied by activation of the barrier-stabilizing GTPases Rac1 and Rap1, as well as inhibition of agonist-induced Ca(2+) mobilization and generation of acto-myosin contractility...
  21. Regier D, Higbee J, Lund K, Sakane F, Prescott S, Topham M. Diacylglycerol kinase iota regulates Ras guanyl-releasing protein 3 and inhibits Rap1 signaling. Proc Natl Acad Sci U S A. 2005;102:7595-600 pubmed
    ..In addition to activating Ras, RasGRP3 also activates Rap1, which in some cases can antagonize the function of Ras...
  22. Dillon T, Carey K, Wetzel S, Parker D, Stork P. Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by the costimulatory molecule CTLA-4. Mol Cell Biol. 2005;25:4117-28 pubmed
    ..We show that the small G protein Rap1 is regulated in the opposite manner; it is inhibited by CD28 and activated by CTLA-4...
  23. Takahashi M, Li Y, Dillon T, Stork P. Phosphorylation of Rap1 by cAMP-dependent Protein Kinase (PKA) Creates a Binding Site for KSR to Sustain ERK Activation by cAMP. J Biol Chem. 2017;292:1449-1461 pubmed publisher
    ..One of the targets of PKA is Rap1 itself, directly phosphorylating Rap1a on serine 180 and Rap1b on serine 179...
  24. Maddala R, Nagendran T, Lang R, Morozov A, Rao P. Rap1 GTPase is required for mouse lens epithelial maintenance and morphogenesis. Dev Biol. 2015;406:74-91 pubmed publisher
    ..While individual germline deficiency of either Rap1a or Rap1b did not cause overt defects in mouse lens, conditional double deficiency (Rap1 cKO) prior to lens placode ..
  25. Maddala R, Chauhan B, Walker C, Zheng Y, Robinson M, Lang R, et al. Rac1 GTPase-deficient mouse lens exhibits defects in shape, suture formation, fiber cell migration and survival. Dev Biol. 2011;360:30-43 pubmed publisher
    ..Lens fiber cell N-cadherin/?-catenin/Rap1/Nectin-based cell-cell junction formation and WAVE-2/Abi-2/Nap1-regulated actin polymerization were impaired in the ..
  26. Kim J, Moon M, Kim H, Li Y, Song D, Kim J, et al. Ras-related GTPases Rap1 and RhoA collectively induce the phagocytosis of serum-opsonized zymosan particles in macrophages. J Biol Chem. 2012;287:5145-55 pubmed publisher
    ..However, 8CPT-2Me-cAMP, an activator of exchange protein directly activated by cAMP (Epac, Rap1 guanine nucleotide exchange factor), restored the phagocytosis of the SOZs that was previously inhibited by the Tat-..
  27. Dower N, Seldin M, Pugh S, Stone J. Organization and chromosomal locations of Rap1a/Krev sequences in the mouse. Mamm Genome. 1992;3:162-7 pubmed
    The human RAP1A gene encodes a protein that apparently can antagonize the function of oncogenic ras genes in gene transfer experiments, but its normal function is unknown...
  28. Le Borgne M, Chartier N, Buchet Poyau K, Destaing O, Faurobert E, Thibert C, et al. The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway. Development. 2014;141:2096-107 pubmed publisher
    ..We further establish that Mex3b acts to regulate the cortical level of activated Rap1, a small G protein controlling phagocytosis and cell-cell interaction, through the activation and transport of ..
  29. Moon M, Kim H, Kim J, Lee J, Kim J, Kim S, et al. Small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-?1. J Cell Physiol. 2013;228:2119-26 pubmed publisher
    ..An activator of Epac (exchange proteins directly activated by cAMP; a guanine nucleotide exchange factor of Rap1), 8CPT-2Me-cAMP which leads to Rap1 activation abrogated MIP-1? expression and macrophage migration...
  30. Königsberger S, Peckl Schmid D, Zaborsky N, Patzak I, Kiefer F, Achatz G. HPK1 associates with SKAP-HOM to negatively regulate Rap1-mediated B-lymphocyte adhesion. PLoS ONE. 2010;5: pubmed publisher
    ..lacking HPK1 after shRNA mediated knockdown exhibit increased basic activation levels of Ras-related protein 1 (Rap1), accompanied by a severe lymphocyte function-associated antigen-1 (LFA-1) dependent homotypic aggregation and ..
  31. Chrzanowska Wodnicka M, White G, Quilliam L, Whitehead K. Small GTPase Rap1 Is Essential for Mouse Development and Formation of Functional Vasculature. PLoS ONE. 2015;10:e0145689 pubmed publisher
    ..As a first step in addressing this question, we present phenotypes of murine total and vascular-specific Rap1a, Rap1b and double Rap1a and Rap1b (Rap1) knockout (KO) mice. The majority of total Rap1 KO mice die before E10...
  32. Cahill M, Bagot R, Gancarz A, Walker D, Sun H, Wang Z, et al. Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron. 2016;89:566-82 pubmed publisher
  33. Obara Y, Horgan A, Stork P. The requirement of Ras and Rap1 for the activation of ERKs by cAMP, PACAP, and KCl in cerebellar granule cells. J Neurochem. 2007;101:470-82 pubmed
    ..Extensive studies in neuronal cell lines have implicated the small G proteins Ras and Rap1 in the activation of ERKs by cAMP, PACAP, and KCl...
  34. Wang Z, Dillon T, Pokala V, Mishra S, Labudda K, Hunter B, et al. Rap1-mediated activation of extracellular signal-regulated kinases by cyclic AMP is dependent on the mode of Rap1 activation. Mol Cell Biol. 2006;26:2130-45 pubmed
    Like other small G proteins of the Ras superfamily, Rap1 is activated by distinct guanine nucleotide exchange factors (GEFs) in response to different signals to elicit cellular responses...
  35. Weissman J, Ma J, Essex A, Gao Y, Burstein E. G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene. 2004;23:241-9 pubmed
    ..A constitutively active mutant of Galphai2 also mediated Ras/rap-dependent responses. These data indicate that GPCRs coupled to pertussis-toxin-sensitive G-proteins activate Rap through a Galpha subunit, C3G, and Src-dependent pathway. ..
  36. Kanemura H, Satoh T, Bilasy S, Ueda S, Hirashima M, Kataoka T. Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1. Biochem Biophys Res Commun. 2009;387:754-9 pubmed publisher
    RA-GEF-1 is a guanine nucleotide exchange factor for the small GTPase Rap1. RA-GEF-1 knockout mice show defects in vascular development starting around 7.5days post coitum and die by 9.5days post coitum...
  37. Potla U, Ni J, Vadaparampil J, Yang G, Leventhal J, Campbell K, et al. Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis-associated glomerular injury. J Clin Invest. 2014;124:1757-69 pubmed publisher
    ..In mouse models, podocyte-specific inactivation of Rap1a and Rap1b induced massive glomerulosclerosis and premature death...
  38. Sabbatini M, Chen X, Ernst S, Williams J. Rap1 activation plays a regulatory role in pancreatic amylase secretion. J Biol Chem. 2008;283:23884-94 pubmed publisher
    ..The current study was designed to determine whether GTP-Rap1 is involved in the regulation of amylase secretion. Rap1A/B and the two Rap1 guanine nucleotide exchange factors, Epac1 and CalDAG-GEF III, were identified in mouse ..
  39. Chrzanowska Wodnicka M. Distinct functions for Rap1 signaling in vascular morphogenesis and dysfunction. Exp Cell Res. 2013;319:2350-9 pubmed publisher
    b>Rap1 signaling is important for both major processes of vessel formation: vasculogenesis, or de novo vessel formation, and angiogenesis, sprouting of new vessels from pre-existing ones...
  40. Jossin Y, Cooper J. Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex. Nat Neurosci. 2011;14:697-703 pubmed publisher
    ..Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are important for multipolar neurons to polarize their migration toward the cortical ..
  41. Kaneko K, Xu P, Cordonier E, Chen S, Ng A, Xu Y, et al. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions. Cell Rep. 2016;16:3003-3015 pubmed publisher
    ..Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (..
  42. Tan R, Lee Y, Chen X. Id-1 plays a key role in cell adhesion in neural stem cells through the preservation of RAP1 signaling. Cell Adh Migr. 2012;6:1-3 pubmed publisher
  43. Kitayama H, Sugimoto Y, Matsuzaki T, Ikawa Y, Noda M. A ras-related gene with transformation suppressor activity. Cell. 1989;56:77-84 pubmed
    ..Thus, the Krev-1 gene seems to play an important role(s) in a wide variety of tissues, and may be involved in the negative growth regulation of certain cell types. ..
  44. Nagai T, Nakamuta S, Kuroda K, Nakauchi S, Nishioka T, Takano T, et al. Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo. Neuron. 2016;89:550-65 pubmed publisher
    ..known and novel PKA substrates downstream of the D1R and obtained more than 100 candidate substrates, including Rap1 GEF (Rasgrp2)...
  45. Côte M, Fos C, Canonigo Balancio A, Ley K, Bécart S, Altman A. SLAT promotes TCR-mediated, Rap1-dependent LFA-1 activation and adhesion through interaction of its PH domain with Rap1. J Cell Sci. 2015;128:4341-52 pubmed publisher
    ..a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B)...
  46. Walkup W, Washburn L, Sweredoski M, Carlisle H, Graham R, Hess S, et al. Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases. J Biol Chem. 2015;290:4908-27 pubmed publisher
    ..Phosphorylation of r-synGAP by CaMKII increases its HRas GAP activity by 25% and its Rap1 GAP activity by 76%...
  47. Stadtmann A, Brinkhaus L, Mueller H, Rossaint J, Bolomini Vittori M, Bergmeier W, et al. Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling. Eur J Immunol. 2011;41:2074-85 pubmed publisher
    ..We found that the small GTPase Rap1 is activated following E-selectin engagement and that blocking Rap1a in Pik3cg-/- mice by a dominant-negative Tat-fusion mutant completely abolished E-selectin-mediated slow rolling...
  48. Sadrian B, Cheng T, Shull O, Gong Q. Rap1gap2 regulates axon outgrowth in olfactory sensory neurons. Mol Cell Neurosci. 2012;50:272-82 pubmed publisher
    ..Rap1gap2 overexpression limits neurite outgrowth and branching in Neuro-2a cells, and counteracts Rap1-induced augmentation of neurite outgrowth...
  49. Bouschet T, Perez V, Fernandez C, Bockaert J, Eychene A, Journot L. Stimulation of the ERK pathway by GTP-loaded Rap1 requires the concomitant activation of Ras, protein kinase C, and protein kinase A in neuronal cells. J Biol Chem. 2003;278:4778-85 pubmed
    ..A (PKA), protein kinase C (PKC), and calcium-dependent signaling; and 2) constitutively active mutants of Rap1, Rap1A-V12, and Rap1B-V12 only minimally stimulated the ERK pathway compared with Ras-V12...
  50. Ni J, Bao S, Johnson R, Zhu B, Li J, Vadaparampil J, et al. MAGI-1 Interacts with Nephrin to Maintain Slit Diaphragm Structure through Enhanced Rap1 Activation in Podocytes. J Biol Chem. 2016;291:24406-24417 pubmed
    ..In cultured podocytes, MAGI-1 depletion reduced intercellular contact-induced Rap1 activation, a pathway critical for proper podocyte function...
  51. Stieglitz B, Bee C, Schwarz D, Yildiz O, Moshnikova A, Khokhlatchev A, et al. Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. EMBO J. 2008;27:1995-2005 pubmed publisher
  52. Mor A, Haklai R, Ben Moshe O, Mekori Y, Kloog Y. Inhibition of contact sensitivity by farnesylthiosalicylic acid-amide, a potential Rap1 inhibitor. J Invest Dermatol. 2011;131:2040-8 pubmed publisher
    We hypothesized that Ras proximate 1 (Rap1) functions as an additional target for farnesylthiosalicylic acid (FTS) or its derivatives, and that the inhibition of Rap1 in lymphocytes by these agents may represent a method for treating ..
  53. Wittchen E, Nishimura E, McCloskey M, Wang H, Quilliam L, Chrzanowska Wodnicka M, et al. Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo. PLoS ONE. 2013;8:e73070 pubmed publisher
    ..Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear...
  54. Awasthi A, Samarakoon A, Chu H, Kamalakannan R, Quilliam L, Chrzanowska Wodnicka M, et al. Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. J Exp Med. 2010;207:1923-38 pubmed publisher
    ..Using Rap1a or Rap1b knockout mice, we identify Rap1b as the major isoform in NK cells...
  55. Mathews C, Dunn B, Hannigan M, Huang C, Leiter E. Genetic control of neutrophil superoxide production in diabetes-resistant ALR/Lt mice. Free Radic Biol Med. 2002;32:744-51 pubmed
  56. Miyata M, Rikitake Y, Takahashi M, Nagamatsu Y, Yamauchi Y, Ogita H, et al. Regulation by afadin of cyclical activation and inactivation of Rap1, Rac1, and RhoA small G proteins at leading edges of moving NIH3T3 cells. J Biol Chem. 2009;284:24595-609 pubmed publisher
    ..We recently showed that another small G protein, Rap1, plays a crucial role in the platelet-derived growth factor (PDGF)-induced formation of leading edge structures and ..
  57. Botelho R, Harrison R, Stone J, Hancock J, Philips M, Jongstra Bilen J, et al. Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis. J Biol Chem. 2009;284:28522-32 pubmed publisher
    We describe a role for diacylglycerol in the activation of Ras and Rap1 at the phagosomal membrane...
  58. Su W, Wynne J, Pinheiro E, Strazza M, Mor A, Montenont E, et al. Rap1 and its effector RIAM are required for lymphocyte trafficking. Blood. 2015;126:2695-703 pubmed publisher
    ..Using mice conditionally deficient in both Rap1a and Rap1b and mice null for RIAM, we show that the Rap1/RIAM module is not required for T- or B-cell development ..
  59. Rah S, Mushtaq M, Nam T, Kim S, Kim U. Generation of cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate by CD38 for Ca2+ signaling in interleukin-8-treated lymphokine-activated killer cells. J Biol Chem. 2010;285:21877-87 pubmed publisher
    ..Furthermore, activation of Rap1, a downstream molecule of Epac, was required for IL-8-induced NAADP formation in LAK cells...
  60. Ferrando I, Chaerkady R, Zhong J, Molina H, Jacob H, Herbst Robinson K, et al. Identification of targets of c-Src tyrosine kinase by chemical complementation and phosphoproteomics. Mol Cell Proteomics. 2012;11:355-69 pubmed publisher
    ..In this context, our study revealed the temporal connection between c-Src activation and the GTPase Rap1, known to stimulate integrin-dependent adhesion...
  61. Miyata M, Ogita H, Komura H, Nakata S, Okamoto R, Ozaki M, et al. Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor. J Cell Sci. 2009;122:4319-29 pubmed publisher
    ..phenotypes were markedly perturbed by knockdown of afadin, and were dependent on the binding of afadin to active Rap1. Binding of Rap1 to afadin was necessary for the recruitment of afadin and the tyrosine phosphatase SHP-2 to the ..
  62. Chang H, Lee J, Poo H, Noda M, Diaz T, Wei B, et al. TIMP-2 promotes cell spreading and adhesion via upregulation of Rap1 signaling. Biochem Biophys Res Commun. 2006;345:1201-6 pubmed
    We previously demonstrated that TIMP-2 treatment of human microvascular endothelial cells (hMVECs) activates Rap1 via the pathway of paxillin-Crk-C3G...
  63. Freeman S, Christian S, Austin P, Iu I, Graves M, Huang L, et al. Applied stretch initiates directional invasion through the action of Rap1 GTPase as a tension sensor. J Cell Sci. 2017;130:152-163 pubmed publisher
    ..applying tensional loads to a three-dimensional collagen gel matrix in culture, is dependent on the Rap1 GTPases (Rap1a and Rap1b, referred to collectively as Rap1)...
  64. Jeyaraj S, Unger N, Eid A, Mitra S, Paul El Dahdah N, Quilliam L, et al. Cyclic AMP-Rap1A signaling activates RhoA to induce ?(2c)-adrenoceptor translocation to the cell surface of microvascular smooth muscle cells. Am J Physiol Cell Physiol. 2012;303:C499-511 pubmed publisher
    ..murine microVSM derived from tail arteries of C57BL6 mice that express functional ?(2C)-ARs and mice deficient in Rap1A (Rap1A-null)...
  65. Schmid M, Franco I, Kang S, Hirsch E, Quilliam L, Varner J. PI3-kinase ? promotes Rap1a-mediated activation of myeloid cell integrin ?4?1, leading to tumor inflammation and growth. PLoS ONE. 2013;8:e60226 pubmed publisher
    ..We show here that PI3K? activates PLC?, leading to RasGrp/CalDAG-GEF-I&II mediated, Rap1a-dependent activation of integrin ?4?1, extravasation of monocytes and granulocytes, and inflammation-associated ..
  66. Lakshmikanthan S, Zheng X, Nishijima Y, Sobczak M, Szabo A, Vasquez Vivar J, et al. Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function. EMBO Rep. 2015;16:628-37 pubmed publisher
    ..The shear stress exerted by flowing blood is the main determinant of NO release. Rap1 promotes integrin- and cadherin-mediated signaling...
  67. Strazza M, Azoulay Alfaguter I, Peled M, Smrcka A, Skolnik E, Srivastava S, et al. PLCε1 regulates SDF-1α-induced lymphocyte adhesion and migration to sites of inflammation. Proc Natl Acad Sci U S A. 2017;114:2693-2698 pubmed publisher
    ..Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1)...
  68. Kondo N, Ueda Y, Kita T, Ozawa M, Tomiyama T, Yasuda K, et al. NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization. Mol Cell Biol. 2017;37: pubmed publisher
    ..in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3...
  69. Schmölders J, Manske C, Otto A, Hoffmann C, Steiner B, Welin A, et al. Comparative Proteomics of Purified Pathogen Vacuoles Correlates Intracellular Replication of Legionella pneumophila with the Small GTPase Ras-related protein 1 (Rap1). Mol Cell Proteomics. 2017;16:622-641 pubmed publisher
    ..The small GTPase Rap1 was identified on D...
  70. Pan B, Vautier F, Ito W, Bolshakov V, Morozov A. Enhanced cortico-amygdala efficacy and suppressed fear in absence of Rap1. J Neurosci. 2008;28:2089-98 pubmed publisher
    ..Here, we report that a CaMKII-alpha-Cre-mediated knock-out (KO) of the rap1a and rap1b genes impaired synaptic plasticity and increased basal synaptic transmission in the cortical but not ..
  71. Aivatiadou E, Ripolone M, Brunetti F, Berruti G. cAMP-Epac2-mediated activation of Rap1 in developing male germ cells: RA-RhoGAP as a possible direct down-stream effector. Mol Reprod Dev. 2009;76:407-16 pubmed publisher
    b>Rap1 is a small GTPase that functions as a positional signal and organizer of cell architecture...
  72. McAvoy T, Zhou M, Greengard P, Nairn A. Phosphorylation of Rap1GAP, a striatally enriched protein, by protein kinase A controls Rap1 activity and dendritic spine morphology. Proc Natl Acad Sci U S A. 2009;106:3531-6 pubmed publisher
    ..We have identified a prominent striatal PKA substrate as Rap1-GTPase activating protein (Rap1GAP), a negative regulator of Rap1 signaling...
  73. Morton A, McManus B, Garside P, Mowat A, Harnett M. Inverse Rap1 and phospho-ERK expression discriminate the maintenance phase of tolerance and priming of antigen-specific CD4+ T cells in vitro and in vivo. J Immunol. 2007;179:8026-34 pubmed
    ..Here, we show that the GTPase Rap1, which can antagonize the generation of such pERK signals and has been reported to accumulate in tolerant cells, ..
  74. Glading A, Ginsberg M. Rap1 and its effector KRIT1/CCM1 regulate beta-catenin signaling. Dis Model Mech. 2010;3:73-83 pubmed publisher
    ..KRIT1 mediates the stabilization of beta-catenin-containing endothelial cell-cell junctions downstream of the Rap1 GTPase...
  75. Subramanian J, Dye L, Morozov A. Rap1 signaling prevents L-type calcium channel-dependent neurotransmitter release. J Neurosci. 2013;33:7245-52 pubmed publisher
    The small GTPase Rap1 contributes to fear learning and cortico-amygdala plasticity by inhibiting glutamate release from cortical neurons, but mechanisms of this inhibition remain unknown...