Gene Symbol: Rap1
Description: RAP1A, member of RAS oncogene family
Alias: C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21, ras-related protein Rap-1A, GTP-binding protein smg p21A, Ras-related protein Krev-1
Species: human
Products:     Rap1

Top Publications

  1. Buss J, Quilliam L, Kato K, Casey P, Solski P, Wong G, et al. The COOH-terminal domain of the Rap1A (Krev-1) protein is isoprenylated and supports transformation by an H-Ras:Rap1A chimeric protein. Mol Cell Biol. 1991;11:1523-30 pubmed
    ..This demonstrates that the modifications and localization signals of the COOH terminus of Rap1A can support the interactions between H-Ras and membranes that are required for transformation. ..
  2. Cullere X, Shaw S, Andersson L, Hirahashi J, Luscinskas F, Mayadas T. Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase. Blood. 2005;105:1950-5 pubmed
    ..b>Rap1, a member of the Ras family of GTPases, is enriched at endothelial cell-cell contacts and activated by cyclic AMP (..
  3. Hogan C, Serpente N, Cogram P, Hosking C, Bialucha C, Feller S, et al. Rap1 regulates the formation of E-cadherin-based cell-cell contacts. Mol Cell Biol. 2004;24:6690-700 pubmed
    ..report here that the cytoplasmic domain of E-cadherin interacts with C3G, a guanine nucleotide exchange factor for Rap1. In epithelial cell cultures, ligation of the extracellular domain of E-cadherin enhances Rap1 activity, which in ..
  4. Li J, O Connor K, Cheng X, Mei F, Uchida T, Townsend C, et al. Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways. Mol Endocrinol. 2007;21:159-71 pubmed
    ..The small GTPase Rap1 can be activated by both PKA and Epac; however, the role of Rap1 in hormone secretion is unknown...
  5. Quinn M, Mullen M, Jesaitis A, Linner J. Subcellular distribution of the Rap1A protein in human neutrophils: colocalization and cotranslocation with cytochrome b559. Blood. 1992;79:1563-73 pubmed
    ..Rap1A is also associated with affinity-purified cytochrome b from unstimulated neutrophils and use specific anti-Rap1 peptide antibodies to biochemically and immunocytochemically determine the subcellular distribution of Rap1A in ..
  6. Gao X, Satoh T, Liao Y, Song C, Hu C, Kariya Ki K, et al. Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras. J Biol Chem. 2001;276:42219-25 pubmed
    ..RA-GEF-1 was identified as a novel Rap GEF, which possesses a Ras/Rap1-associating (RA) domain. Here we report a protein closely related to RA-GEF-1, named RA-GEF-2...
  7. Mochizuki N, Yamashita S, Kurokawa K, Ohba Y, Nagai T, Miyawaki A, et al. Spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Nature. 2001;411:1065-8 pubmed
    ..transfer)-based sensors to report on the spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Epidermal growth factor activated Ras at the peripheral plasma membrane and Rap1 at the intracellular perinuclear ..
  8. Boettner B, Govek E, Cross J, Van Aelst L. The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin. Proc Natl Acad Sci U S A. 2000;97:9064-9 pubmed
    ..We further demonstrate that both Ras and Rap1 interact with full-length AF-6 in vivo in mammalian cells and that a fraction of Rap1 colocalizes with AF-6 at the ..
  9. Serebriiskii I, Estojak J, Sonoda G, Testa J, Golemis E. Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22. Oncogene. 1997;15:1043-9 pubmed
    ..Intriguingly, the Krit cDNA has been mapped by FISH to chromosome 7q21-22, a region known to be frequently deleted or amplified in multiple forms of cancer. ..

More Information


  1. Ahmed S, Daulat A, Meunier A, Angers S. G protein betagamma subunits regulate cell adhesion through Rap1a and its effector Radil. J Biol Chem. 2010;285:6538-51 pubmed publisher
    ..These results add to the molecular understanding of how G protein-coupled receptors impinge on cell adhesion and suggest that the Gbetagamma x Rap1 x Radil complex plays important roles in this process.
  2. Castro A, Rebhun J, Clark G, Quilliam L. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem. 2003;278:32493-6 pubmed
    ..Because of the homology of TSC2 with GTPase-activating proteins for Rap1, we examined whether a Ras/Rap-related GTPase might be involved in this process...
  3. Arthur W, Quilliam L, Cooper J. Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. J Cell Biol. 2004;167:111-22 pubmed
    The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading in various mammalian cell types...
  4. Chen C, Chuang H, Huang C, Fang F, Huang H, Tsai H, et al. Overexpression of Rap-1A indicates a poor prognosis for oral cavity squamous cell carcinoma and promotes tumor cell invasion via Aurora-A modulation. Am J Pathol. 2013;182:516-28 pubmed publisher
    ..Taken together, our results suggest that the Aurora-A/Rap-1A pathway is associated with survival, tumor progression, and metastasis of OCSCC patients. ..
  5. Lafuente E, Iwamoto Y, Carman C, Van Puijenbroek A, Constantine E, Li L, et al. Active Rap1, a small GTPase that induces malignant transformation of hematopoietic progenitors, localizes in the nucleus and regulates protein expression. Leuk Lymphoma. 2007;48:987-1002 pubmed
    b>Rap1, a member of the Ras superfamily, regulates cytoskeletal changes in lower eukaryots and integrin-mediated adhesion in hematopoietic cells...
  6. 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
    ..We show herein that the Ras family GTPase Rap1 has a key role in the regulation of angiogenesis by modulating endothelial cell functions...
  7. Rebhun J, Castro A, Quilliam L. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. J Biol Chem. 2000;275:34901-8 pubmed
    ..of these GEFs, MR-GEF (M-Ras-regulated GEF, KIAA0277) and PDZ-GEF (KIAA0313) bound specifically to nucleotide-free Rap1 and Rap1/Rap2, respectively. Both proteins functioned as Rap1 GEFs in vivo...
  8. de Rooij J, Rehmann H, van Triest M, Cool R, Wittinghofer A, Bos J. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J Biol Chem. 2000;275:20829-36 pubmed
    ..and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well...
  9. 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...
  10. Sehrawat S, Cullere X, Patel S, Italiano J, Mayadas T. Role of Epac1, an exchange factor for Rap GTPases, in endothelial microtubule dynamics and barrier function. Mol Biol Cell. 2008;19:1261-70 pubmed publisher
    b>Rap1 GTPase activation by its cAMP responsive nucleotide exchange factor Epac present in endothelial cells increases endothelial cell barrier function with an associated increase in cortical actin...
  11. Su L, Hattori M, Moriyama M, Murata N, Harazaki M, Kaibuchi K, et al. AF-6 controls integrin-mediated cell adhesion by regulating Rap1 activation through the specific recruitment of Rap1GTP and SPA-1. J Biol Chem. 2003;278:15232-8 pubmed
    In the present study, we showed that SPA-1, a Rap1 GTPase-activating protein (GAP), was bound to a cytoskeleton-anchoring protein AF-6...
  12. Dao V, Dupuy A, Gavet O, Caron E, de Gunzburg J. Dynamic changes in Rap1 activity are required for cell retraction and spreading during mitosis. J Cell Sci. 2009;122:2996-3004 pubmed publisher
    ..Because of the well-documented ability of the small GTPase Rap1 to stimulate integrin-dependent adhesion and spreading, we assessed its role during mitosis...
  13. 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. ..
  14. Béraud Dufour S, Gautier R, Albiges Rizo C, Chardin P, Faurobert E. Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1. FEBS J. 2007;274:5518-32 pubmed
    The small G protein Rap1 regulates diverse cellular processes such as integrin activation, cell adhesion, cell-cell junction formation and cell polarity...
  15. Katagiri K, Maeda A, Shimonaka M, Kinashi T. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nat Immunol. 2003;4:741-8 pubmed
    The small GTPase Rap1 is a potent activator of leukocyte integrin. However, the regulatory mechanism involved is unknown. Here, we identify the Rap1 effector, RAPL, as an essential regulator in this activation...
  16. Pannekoek W, van Dijk J, Chan O, Huveneers S, Linnemann J, Spanjaard E, et al. Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control. Cell Signal. 2011;23:2056-64 pubmed publisher
    Epac1 and its effector Rap1 are important mediators of cAMP induced tightening of endothelial junctions and consequential increased barrier function...
  17. Fukuhara S, Sakurai A, Sano H, Yamagishi A, Somekawa S, Takakura N, et al. Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway. Mol Cell Biol. 2005;25:136-46 pubmed
    ..a specific activator for Epac, which is a novel cAMP-dependent guanine nucleotide exchange factor for Rap1. Thus, we investigated the effect of Rap1 on permeability and the VE-cadherin-mediated cell adhesion by expressing ..
  18. Jeong H, Li Z, Brown M, Sacks D. IQGAP1 binds Rap1 and modulates its activity. J Biol Chem. 2007;282:20752-62 pubmed
    ..Here we show that IQGAP1 also binds to the small GTPase Rap1. In vitro analysis demonstrates a direct interaction between Rap1 and IQGAP1, which is augmented by activation (GTP ..
  19. Doebele R, Schulze Hoepfner F, Hong J, Chlenski A, Zeitlin B, Goel K, et al. A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis. Blood. 2009;114:4592-600 pubmed publisher
    ..Epac is a cyclic adenosine 5'-monophosphate-activated guanine nucleotide exchange factor for Rap1. In this study, we show that activation of Epac or Rap1 leads to potent inhibition of angiogenesis in vivo...
  20. Wittchen E, Worthylake R, Kelly P, Casey P, Quilliam L, Burridge K. Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function. J Biol Chem. 2005;280:11675-82 pubmed
    ..Here we show that activation of the Rap1 GTPase in endothelial cells accelerated de novo assembly of endothelial cell-cell junctions and increased the ..
  21. Ghandour H, Cullere X, Alvarez A, Luscinskas F, Mayadas T. Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood. 2007;110:3682-90 pubmed
    ..The small GTPase Rap1 is a critical activator of both integrins in murine lymphocytes and T-cell lines...
  22. Lee H, Lim C, Puzon McLaughlin W, Shattil S, Ginsberg M. RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. J Biol Chem. 2009;284:5119-27 pubmed publisher
    b>Rap1 small GTPases interact with Rap1-GTP-interacting adaptor molecule (RIAM), a member of the MRL (Mig-10/RIAM/Lamellipodin) protein family, to promote talin-dependent integrin activation...
  23. Pizon V, Chardin P, Lerosey I, Olofsson B, Tavitian A. Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region. Oncogene. 1988;3:201-4 pubmed
    We have characterized two new ras-related genes rap1 and rap2 from a human cDNA library, by hybridization with the Drosophila Dras3 gene at low stringency conditions...
  24. Kuiperij H, de Rooij J, Rehmann H, van Triest M, Wittinghofer A, Bos J, et al. Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2. Biochim Biophys Acta. 2003;1593:141-9 pubmed
    ..PDZ-GEF1 efficiently exchanges nucleotides of both Rap1 and Rap2, but has also been implicated in mediating cAMP-induced Ras activation through binding of cAMP to the RCBD...
  25. Hattori M, Minato N. Rap1 GTPase: functions, regulation, and malignancy. J Biochem. 2003;134:479-84 pubmed
    b>Rap1 is a member of the Ras family of small GTPases that is activated by diverse extracellular stimuli in many cell types...
  26. Glading A, Han J, Stockton R, Ginsberg M. KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J Cell Biol. 2007;179:247-54 pubmed
    ..KRIT-1 binds to Rap1, a guanosine triphosphatase that maintains the integrity of endothelial junctions...
  27. Kurooka T, Yamamoto Y, Takai Y, Sakisaka T. Dual regulation of RA-RhoGAP activity by phosphatidic acid and Rap1 during neurite outgrowth. J Biol Chem. 2011;286:6832-43 pubmed publisher
    ..previously identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as a direct downstream target of Rap1 small G protein in the neurite outgrowth...
  28. 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
    Ras-associated protein 1 (Rap1), a small GTPase, attracted attention because of its involvement in several aspects of cell adhesion, including integrin- and cadherin-mediated adhesion...
  29. Bivona T, Wiener H, Ahearn I, Silletti J, Chiu V, Philips M. Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. J Cell Biol. 2004;164:461-70 pubmed
    b>Rap1 and Ras are closely related GTPases that share some effectors but have distinct functions. We studied the subcellular localization of Rap1 and its sites of activation in living cells...
  30. Lafuente E, Van Puijenbroek A, Krause M, Carman C, Freeman G, Berezovskaya A, et al. RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Dev Cell. 2004;7:585-95 pubmed
    The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule...
  31. Fujita H, Fukuhara S, Sakurai A, Yamagishi A, Kamioka Y, Nakaoka Y, et al. Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes. J Biol Chem. 2005;280:5022-31 pubmed
    ..Here we report that Rap1 controls the migration of vascular endothelial cells...
  32. 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...
  33. Riedl J, Brandt D, Batlle E, Price L, Clevers H, Bos J. Down-regulation of Rap1 activity is involved in ephrinB1-induced cell contraction. Biochem J. 2005;389:465-9 pubmed
    ..On ephrinB1 stimulation, the small GTPases Rho and Ras are activated and Rap1 is inactivated...
  34. Wang H, Han X, Bretz C, Becker S, Gambhir D, Smith G, et al. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization. Mol Ther Methods Clin Dev. 2016;3:16056 pubmed publisher
    ..to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, ..
  35. Lagarrigue F, Kim C, Ginsberg M. The Rap1-RIAM-talin axis of integrin activation and blood cell function. Blood. 2016;128:479-87 pubmed publisher
    ..Second, we review our understanding of how signaling events, particularly those involving Rap1 small guanosine triphosphate (GTP)hydrolases, can regulate the talin-integrin interaction and resulting activation...
  36. Gaullier G, Miron S, Pisano S, Buisson R, Le Bihan Y, Tellier Lebègue C, et al. A higher-order entity formed by the flexible assembly of RAP1 with TRF2. Nucleic Acids Res. 2016;44:1962-76 pubmed publisher
    ..Within shelterin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of ..
  37. Kawata M, Matsui Y, Kondo J, Hishida T, Teranishi Y, Takai Y. A novel small molecular weight GTP-binding protein with the same putative effector domain as the ras proteins in bovine brain membranes. Purification, determination of primary structure, and characterization. J Biol Chem. 1988;263:18965-71 pubmed
    ..007 min-1. These kinetic properties of smg p21 are similar to those of the c-ras proteins. These results suggest that smg p21 is a novel GTP-binding protein exerting action(s) similar or antagonistic to that (those) of the ras proteins. ..
  38. Yang B, Wang H, Gao X, Chen B, Zhang Y, Liu H, et al. Expression and significance of Rap1A in testes of azoospermic subjects. Asian J Androl. 2004;6:35-40 pubmed
    ..The mRNA expression of Rap1A in the spermatogenic cells of azoospermic was stronger than that in those of the fertile testes. Rap1A may play certain roles in the development of azoospermia. ..
  39. Bokoch G, Parkos C, Mumby S. Purification and characterization of the 22,000-dalton GTP-binding protein substrate for ADP-ribosylation by botulinum toxin, G22K. J Biol Chem. 1988;263:16744-9 pubmed
    ..G22K appears to be a unique GTP-binding protein which serves as a substrate for ADP-ribosylation by a component of botulinum toxin and which may be involved in exocytotic secretion or cellular differentiation. ..
  40. Balzac F, Avolio M, Degani S, Kaverina I, Torti M, Silengo L, et al. E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function. J Cell Sci. 2005;118:4765-83 pubmed
    ..Here, we demonstrate that the small GTPase Rap1, a crucial regulator of the inside-out activation of integrins, is a target for E-cadherin-mediated outside-in ..
  41. Lin Y, Ke C, Wang Y, Chen M, Chen T, Ku W, et al. RAB10 Interacts with the Male Germ Cell-Specific GTPase-Activating Protein during Mammalian Spermiogenesis. Int J Mol Sci. 2017;18: pubmed publisher
    ..g., RAB10, RAB5C, and RAP1), were identified using co-immunoprecipitation (co-IP) and nano liquid chromatography-mass spectrometry/mass ..
  42. Ding Y, Liang X, Zhang Y, Yi L, Shum H, Chen Q, et al. Rap1 deficiency-provoked paracrine dysfunction impairs immunosuppressive potency of mesenchymal stem cells in allograft rejection of heart transplantation. Cell Death Dis. 2018;9:386 pubmed publisher
    ..This study aimed to elucidate the role of Rap1 (repressor/activator protein), a novel modulator involved in the NF-κB pathway, in regulating the ..
  43. Larcher M, Pasquier E, MacDonald R, Wellinger R. Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends. PLoS Genet. 2016;12:e1006479 pubmed publisher
    ..After repair, the yKu-distal portion of telomeres is bound by Rap1, which in turn reduces the potential for yKu to mediate NHEJ...
  44. Berrou E, Adam F, Lebret M, Planche V, Fergelot P, Issertial O, et al. Gain-of-Function Mutation in Filamin A Potentiates Platelet Integrin ?IIb?3 Activation. Arterioscler Thromb Vasc Biol. 2017;37:1087-1097 pubmed publisher
    ..integrin activation and a parallel increase in talin recruitment to ?3, contrasting with normal Rap1 activation...
  45. Bergom C, Hauser A, Rymaszewski A, Gonyo P, Prokop J, Jennings B, et al. The Tumor-suppressive Small GTPase DiRas1 Binds the Noncanonical Guanine Nucleotide Exchange Factor SmgGDS and Antagonizes SmgGDS Interactions with Oncogenic Small GTPases. J Biol Chem. 2016;291:6534-45 pubmed publisher
    ..Taken together, our data support a model in which DiRas1 expression inhibits malignant features of cancers in part by nonproductively binding to SmgGDS and inhibiting the binding of other small GTPases to SmgGDS. ..
  46. 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
    ..through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B)...
  47. Delehanty L, Mogass M, Gonias S, Racke F, Johnstone B, Goldfarb A. Stromal inhibition of megakaryocytic differentiation is associated with blockade of sustained Rap1 activation. Blood. 2003;101:1744-51 pubmed
    ..Because stromal contact blocked delayed but not early ERK activation, the small guanosine triphosphatase (GTPase) Rap1 was considered as a candidate inhibitory target...
  48. Takai S, Nishino N, Kitayama H, Ikawa Y, Noda M. Mapping of the KREV1 transformation suppressor gene and its pseudogene (KREV1P) to human chromosome 1p13.3 and 14q24.3, respectively, by fluorescence in situ hybridization. Cytogenet Cell Genet. 1993;63:59-61 pubmed
    The chromosomal location of the transformation suppressor gene KREV1 and its pseudogene (KREV1P) on R-banded human prometaphase chromosomes was determined by fluorescence in situ hybridization. The KREV1 gene mapped to chromosome 1p13...
  49. Nomura K, Kanemura H, Satoh T, Kataoka T. Identification of a novel domain of Ras and Rap1 that directs their differential subcellular localizations. J Biol Chem. 2004;279:22664-73 pubmed
    ..of a series of Ha-Ras-Rap1A chimeras shows that Ha-Ras carrying a replacement of amino acids 46-101 with that of Rap1 exhibits the perinuclear localization...
  50. Mitra R, Zhang Z, Henson B, Kurnit D, Carey T, D Silva N. Rap1A and rap1B ras-family proteins are prominently expressed in the nucleus of squamous carcinomas: nuclear translocation of GTP-bound active form. Oncogene. 2003;22:6243-56 pubmed
    We recently showed that rap1 regulates growth and proliferation in normal keratinocytes, which provoked us to investigate its expression and regulation in malignant cells...
  51. Okada T, Hu C, Jin T, Kariya K, Yamawaki Kataoka Y, Kataoka T. The strength of interaction at the Raf cysteine-rich domain is a critical determinant of response of Raf to Ras family small GTPases. Mol Cell Biol. 1999;19:6057-64 pubmed
    ..These results indicate that the strength of interaction with Ras and Rap1A at its CRD may be a critical determinant of regulation of the Raf kinase activity by the Ras family small GTPases. ..
  52. Lee K, Kobayashi Y, Seo H, Kwak J, Masuda A, Lim C, et al. Involvement of cAMP-guanine nucleotide exchange factor II in hippocampal long-term depression and behavioral flexibility. Mol Brain. 2015;8:38 pubmed publisher
    ..II (cAMP-GEF II) acts as a target for cAMP independently of protein kinase A (PKA) and functions as a GEF for Rap1 and Rap2...
  53. Isobe S, Nagao K, Nozaki N, Kimura H, Obuse C. Inhibition of RIF1 by SCAI Allows BRCA1-Mediated Repair. Cell Rep. 2017;20:297-307 pubmed publisher
    ..RIF1 (RAP1-interacting factor homolog) was recently shown to stimulate NHEJ through an interaction with 53BP1 (p53-binding ..
  54. Umezawa Y, Akiyama H, Okada K, Ishida S, Nogami A, Oshikawa G, et al. Molecular mechanisms for enhancement of stromal cell-derived factor 1-induced chemotaxis by platelet endothelial cell adhesion molecule 1 (PECAM-1). J Biol Chem. 2017;292:19639-19655 pubmed publisher
    ..respectively, SDF-1-induced G?i-dependent activation of the PI3K/Akt/mTORC1 pathway and small GTPase Rap1 in hematopoietic 32Dcl3 cells, and these changes in activation correlated with chemotaxis...
  55. Reilly J, Neighbors J, Hohl R. Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer metastasis. Cancer Biol Ther. 2017;18:872-882 pubmed publisher
    ..Our findings reiterate a role for protein geranylgeranylation in the development of prostate cancer metastasis in vivo...
  56. Lee J, Ryu Y, Ji Y, Kang J, Moon E. Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4. Oncotarget. 2015;6:9820-33 pubmed
    Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis...
  57. Gomez G, McLachlan R, Wu S, Caldwell B, Moussa E, Verma S, et al. An RPTPα/Src family kinase/Rap1 signaling module recruits myosin IIB to support contractile tension at apical E-cadherin junctions. Mol Biol Cell. 2015;26:1249-62 pubmed publisher
    ..Further, we identify a receptor type-protein tyrosine phosphatase alpha-Src family kinase-Rap1 pathway as responsible for recruiting myosin IIB to the ZA and supporting contractile tension...
  58. Law D, Nannizzi Alaimo L, Phillips D. Outside-in integrin signal transduction. Alpha IIb beta 3-(GP IIb IIIa) tyrosine phosphorylation induced by platelet aggregation. J Biol Chem. 1996;271:10811-5 pubmed
    ..The data suggest that tyrosine phosphorylation of an integrin beta subunit may be important in initiating outside-in signaling cascades by inducing association of signaling components directly with the integrin. ..
  59. Schippers M, Beljaars L, Post E, Lotersztajn S, Reker Smit C, Han B, et al. Upregulation of Epac-1 in Hepatic Stellate Cells by Prostaglandin E2 in Liver Fibrosis Is Associated with Reduced Fibrogenesis. J Pharmacol Exp Ther. 2017;363:126-135 pubmed publisher
    ..In primary isolated HSC, PGE2 elicited Rap1 translocation reflecting Epac-1 activation, and Epac-1 agonists attenuated platelet-derived growth factor-induced ..
  60. Kovacs Kasa A, Kim K, Cherian Shaw M, Black S, Fulton D, Verin A. Extracellular adenosine-induced Rac1 activation in pulmonary endothelium: molecular mechanisms and barrier-protective role. J Cell Physiol. 2017;: pubmed publisher
    ..We next examined the role of cAMP-activated Epac1 and its putative downstream targets Rac1, Vav2, Rap1 and Tiam1. Depletion of Epac1 attenuated the adenosine-induced Rac1 activation and the increase in TER...
  61. McColl B, Garg R, Riou P, Riento K, Ridley A. Rnd3-induced cell rounding requires interaction with Plexin-B2. J Cell Sci. 2016;129:4046-4056 pubmed
    ..Plexin-B1 has been reported to act as a GAP for R-Ras and/or Rap1 proteins...
  62. Prevost N, Woulfe D, Tognolini M, Tanaka T, Jian W, Fortna R, et al. Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1. Blood. 2004;103:1348-55 pubmed
    ..It also enhances Rap1 activation without requiring ADP secretion, ephrinB1 phosphorylation, or the activation of PI3-kinase and Src...
  63. Zhu L, Yang J, Bromberger T, Holly A, Lu F, Liu H, et al. Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nat Commun. 2017;8:1744 pubmed publisher
    ..Membrane-anchored mammalian small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to be weak and thus hardly studied...
  64. Klinger M, Kudlacek O, Seidel M, Freissmuth M, Sexl V. MAP kinase stimulation by cAMP does not require RAP1 but SRC family kinases. J Biol Chem. 2002;277:32490-7 pubmed
    The small G protein RAP1 and the kinase B-RAF have been proposed to link elevations of cAMP to activation of ERK/mitogen-activated protein (MAP) kinase...
  65. Seino S, Takahashi H, Takahashi T, Shibasaki T. Treating diabetes today: a matter of selectivity of sulphonylureas. Diabetes Obes Metab. 2012;14 Suppl 1:9-13 pubmed publisher
    ..SUs are now known also to activate cAMP sensor Epac2 (cAMP-GEFII) to Rap1 signalling, which promotes insulin granule exocytosis...
  66. Guo X, An S, Yang Y, Liu Y, Hao Q, Xu T. Rap-Interacting Proteins are Key Players in the Rap Symphony Orchestra. Cell Physiol Biochem. 2016;39:137-56 pubmed publisher
  67. Hoggard T, Liachko I, Burt C, Meikle T, Jiang K, Craciun G, et al. High Throughput Analyses of Budding Yeast ARSs Reveal New DNA Elements Capable of Conferring Centromere-Independent Plasmid Propagation. G3 (Bethesda). 2016;6:993-1012 pubmed publisher
    ..The Rap1 protein-binding site (RAP1) present in transcriptional silencers and telomeres of budding yeast is a known plasmid-..
  68. Frech M, John J, Pizon V, Chardin P, Tavitian A, Clark R, et al. Inhibition of GTPase activating protein stimulation of Ras-p21 GTPase by the Krev-1 gene product. Science. 1990;249:169-71 pubmed
    ..This may occur by preventing interaction of GAP with Ras-p21 or with other cellular proteins necessary for GAP-mediated Ras GTPase activity. ..
  69. Hashimoto N, Hamamura K, Kotani N, Furukawa K, Kaneko K, Honke K, et al. Proteomic analysis of ganglioside-associated membrane molecules: substantial basis for molecular clustering. Proteomics. 2012;12:3154-63 pubmed publisher
    ..Representative examples of GD3-associated molecules such as neogenin and MCAM were shown...
  70. Wang J, Lee J, Christian S, Dang Lawson M, Pritchard C, Freeman S, et al. The Rap1-cofilin-1 pathway coordinates actin reorganization and MTOC polarization at the B cell immune synapse. J Cell Sci. 2017;130:1094-1109 pubmed publisher
    ..We now show that BCR-induced MTOC polarization requires the Rap1 GTPase (which has two isoforms, Rap1a and Rap1b), an evolutionarily conserved regulator of cell polarity, as well ..
  71. 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 ..
  72. Song Z, Bakeer W, Marshall J, Yakasai A, Khalid R, Collemare J, et al. Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae. Chem Sci. 2015;6:4837-4845 pubmed publisher
    The ACE1 and RAP1 genes from the avirulence signalling gene cluster of the rice blast fungus Magnaporthe oryzae were expressed in Aspergillus oryzae and M. oryzae itself...
  73. Liu L, Aerbajinai W, Ahmed S, Rodgers G, Angers S, Parent C. Radil controls neutrophil adhesion and motility through ?2-integrin activation. Mol Biol Cell. 2012;23:4751-65 pubmed publisher
    ..We show that Radil, a novel Rap1 effector, regulates ?1- and ?2-integrin activation and controls neutrophil chemotaxis...