Gene Symbol: Rap1b
Description: RAS related protein 1b
Alias: 2810443E11Rik, ras-related protein Rap-1b, GTP-binding protein smg p21B
Species: mouse
Products:     Rap1b

Top Publications

  1. 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
  2. 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...
  3. Chu H, Awasthi A, White G, Chrzanowska Wodnicka M, Malarkannan S. Rap1b regulates B cell development, homing, and T cell-dependent humoral immunity. J Immunol. 2008;181:3373-83 pubmed
    ..Rap1 exists in two isoforms: Rap1a and Rap1b. Although Rap1 has been extensively studied, its isoform-specific functions in B cells have not been elucidated...
  4. 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...
  5. Chrzanowska Wodnicka M, Smyth S, Schoenwaelder S, Fischer T, White G. Rap1b is required for normal platelet function and hemostasis in mice. J Clin Invest. 2005;115:680-7 pubmed
    b>Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists...
  6. Chrzanowska Wodnicka M, Kraus A, Gale D, White G, Vansluys J. Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice. Blood. 2008;111:2647-56 pubmed
    ..Here we identify a small GTPase, Rap1b, as a positive regulator of angiogenesis...
  7. 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. ..
  8. Carbo C, Duerschmied D, Goerge T, Hattori H, Sakai J, Cifuni S, et al. Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis. J Leukoc Biol. 2010;88:313-9 pubmed publisher
    ..Here, we explored the role of CalDAG-GEFI and Rap1b in integrin-independent neutrophil chemotaxis...
  9. 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
    ..Rap1a and Rap1b, 2 highly homologous small G proteins, are both required for angiogenesis in vivo and for normal EC responses to ..

More Information


  1. 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 ..
  2. Wang Z, Holly S, Larson M, Liu J, Yuan W, Chrzanowska Wodnicka M, et al. Rap1b is critical for glycoprotein VI-mediated but not ADP receptor-mediated alpha2beta1 activation. J Thromb Haemost. 2009;7:693-700 pubmed publisher
    ..A strong candidate molecule is the small GTPase Rap1b, the dominant platelet isoform of Rap1, which regulates alphaIIbbeta3 activation...
  3. Takahashi M, Rikitake Y, Nagamatsu Y, Hara T, Ikeda W, Hirata K, et al. Sequential activation of Rap1 and Rac1 small G proteins by PDGF locally at leading edges of NIH3T3 cells. Genes Cells. 2008;13:549-69 pubmed publisher
    ..This process is pivotal for the PDGF-induced formation of leading edge structures and cell movement. ..
  4. Zhang G, Xiang B, Ye S, Chrzanowska Wodnicka M, Morris A, Gartner T, et al. Distinct roles for Rap1b protein in platelet secretion and integrin ?IIb?3 outside-in signaling. J Biol Chem. 2011;286:39466-77 pubmed publisher
    b>Rap1b is activated by platelet agonists and plays a critical role in integrin ?(IIb)?(3) inside-out signaling and platelet aggregation...
  5. Bernardi B, Guidetti G, Campus F, Crittenden J, Graybiel A, Balduini C, et al. The small GTPase Rap1b regulates the cross talk between platelet integrin alpha2beta1 and integrin alphaIIbbeta3. Blood. 2006;107:2728-35 pubmed
    The involvement of the small GTPase Rap1b in platelet integrin alpha2beta1-dependent outside-in signaling was investigated...
  6. Kumar S, Xu J, Kumar R, Lakshmikanthan S, Kapur R, Kofron M, et al. The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. J Exp Med. 2014;211:1741-58 pubmed publisher
    ..The small GTPase Rap1b is generally viewed as a positive regulator of immune cell functions by controlling bidirectional integrin ..
  7. 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 but is ..
  8. 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
    ..This Rap1-dependent regulation of T-cell circulation prevents the onset of colitis. ..
  9. Shah B, Lutter D, Tsytsyura Y, Glyvuk N, Sakakibara A, Klingauf J, et al. Rap1 GTPases Are Master Regulators of Neural Cell Polarity in the Developing Neocortex. Cereb Cortex. 2017;27:1253-1269 pubmed publisher
    ..Taken together, the loss of RGC and neuronal polarity results in the disruption of cortical organization. ..
  10. 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. ..
  11. 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
    ..Rap1 activation not only mediates the cAMP-evoked response via Epac1 but is also involved in CCK- and carbachol-induced amylase release, with their action most likely mediated by CalDAG-GEF III. ..
  12. Ozaki N, Shibasaki T, Kashima Y, Miki T, Takahashi K, Ueno H, et al. cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol. 2000;2:805-11 pubmed
    ..Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis. ..
  13. 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
    ..b>Rap1B isoforms is less clear...
  14. Stefanini L, Paul D, Robledo R, Chan E, Getz T, Campbell R, et al. RASA3 is a critical inhibitor of RAP1-dependent platelet activation. J Clin Invest. 2015;125:1419-32 pubmed publisher
    ..These findings provide insight into the antithrombotic effect of P2Y12 inhibitors and may lead to improved diagnosis and treatment of platelet-related disorders. ..
  15. Subramanian J, Dye L, Morozov A. Rap1 signaling prevents L-type calcium channel-dependent neurotransmitter release. J Neurosci. 2013;33:7245-52 pubmed publisher
    ..We propose that the Rap1 signaling enables plasticity and fear learning by regulating LTCCs at cortico-amygdala synapses. ..
  16. 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
    ..Taken together, our results suggest that Dab2IP plays an important role in the migration and positioning of a subpopulation of later-born (layers II-IV) neurons, likely through the regulation of Rap1 and integrin signaling. ..
  17. 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
    ..Our results demonstrate that sema3e/plexin D1 modulates IS formation and Ag-scanning activities of thymocytes within thymic tissues. ..
  18. 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...
  19. Ribeiro Neto F, Leon A, Urbani Brocard J, Lou L, Nyska A, Altschuler D. cAMP-dependent oncogenic action of Rap1b in the thyroid gland. J Biol Chem. 2004;279:46868-75 pubmed
    cAMP signaling leads to activation and phosphorylation of Rap1b. Using cellular models where cAMP stimulates cell proliferation, we have demonstrated that cAMP-mediated activation, as well as phosphorylation of Rap1b, is critical for ..
  20. Zou W, Izawa T, Zhu T, Chappel J, Otero K, Monkley S, et al. Talin1 and Rap1 are critical for osteoclast function. Mol Cell Biol. 2013;33:830-44 pubmed publisher
    ..Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss. ..
  21. 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
  22. Traver S, Bidot C, Spassky N, Baltauss T, de Tand M, Thomas J, et al. RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao. Biochem J. 2000;350 Pt 1:19-29 pubmed
  23. 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
    ..These findings demonstrate a novel DA-PKA-Rap1-MAPK intracellular signaling mechanism in D1R-MSNs that increases neuronal excitability to enhance reward-related behaviors. ..
  24. 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
    ..Our findings reveal key roles for the bidirectional synaptic expression of the Rap1b small GTPase and an associated local synaptic protein translation network in this process...
  25. Chen Y, Yu M, Podd A, Wen R, Chrzanowska Wodnicka M, White G, et al. A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development. Blood. 2008;111:4627-36 pubmed publisher
    ..Rap1 is a member of the Ras superfamily of small GTP-binding proteins and has 2 isoforms, Rap1a and Rap1b. Although Rap1 has been suggested to have an important role in a variety of cellular processes, no direct evidence ..
  26. 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
    ..Our findings reveal crucial roles for Rap1 signaling via NDR1 for recruitment of kindlin-3 and IS organization. ..
  27. Lakshmikanthan S, Zieba B, Ge Z, Momotani K, Zheng X, Lund H, et al. Rap1b in smooth muscle and endothelium is required for maintenance of vascular tone and normal blood pressure. Arterioscler Thromb Vasc Biol. 2014;34:1486-94 pubmed publisher
    Small GTPase Ras-related protein 1 (Rap1b) controls several basic cellular phenomena, and its deletion in mice leads to several cardiovascular defects, including impaired adhesion of blood cells and defective angiogenesis...
  28. 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...
  29. Sun L, Xie P, Wada J, Kashihara N, Liu F, Zhao Y, et al. Rap1b GTPase ameliorates glucose-induced mitochondrial dysfunction. J Am Soc Nephrol. 2008;19:2293-301 pubmed publisher
    ..The GTPase Ras-proximate-1 (Rap1b) is upregulated in the hyperglycemic state and is known to increase B-Raf, an antiapoptotic effector protein...
  30. 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
    ..of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B)...
  31. 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 thalamic ..
  32. 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
    ..Our study establishes a novel paradigm for Rap1 as a regulator of mechanotransduction. ..
  33. Chavrier P, Simons K, Zerial M. The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach. Gene. 1992;112:261-4 pubmed
    ..These results confirm that the overall diversity of the Rab and Rho protein subfamilies account for more than thirty different members in mammalian cells. ..
  34. 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
    ..Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment. ..
  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. ..