Affinage

RAP1B

Ras-related protein Rap-1b · UniProt P61224

Length
184 aa
Mass
20.8 kDa
Annotated
2026-04-28
100 papers in source corpus 52 papers cited in narrative 52 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAP1B is a membrane-anchored small GTPase that functions as a central integrator of inside-out integrin activation, cytoskeletal remodeling, and MAPK signaling across diverse cell types including platelets, immune cells, neurons, and endothelium. GTP-loaded RAP1B, generated by GEFs including CalDAG-GEFI (Ca²⁺/DAG-dependent), C3G (via Crkl/VASP), and EPAC (cAMP-dependent), engages effectors such as talin (recruiting it to membranes for integrin αIIbβ3 activation), B-Raf (stimulating the MEK–ERK cascade), IQGAP1 (scaffolding B-Raf/C-Raf/ERK in NK cells), and RalA/PI3K (specifying axonal identity), while its activity is terminated by PKA/PKG phosphorylation on Ser179, which allosterically distorts switch I/II loops, impairs SmgGDS-dependent prenylation and membrane targeting, and indirectly blocks CalDAG-GEFI-mediated activation (PMID:18660803, PMID:29170462, PMID:10224142, PMID:19651783, PMID:23716716, PMID:8576107, PMID:15286792, PMID:20733035, PMID:24165023). Genetic knockout in mice demonstrates that RAP1B is required for platelet aggregation and hemostasis, NK-cell cytotoxicity, B-cell adhesion and homing, neutrophil migration restraint, vascular tone maintenance via NO-dependent vasodilation, endothelial barrier dynamics, and skeletal morphogenesis (PMID:15696195, PMID:18714009, PMID:25092872, PMID:24790136, PMID:29222111, PMID:28520221). In neurons, Smurf2-mediated ubiquitination and proteasomal degradation of inactive RAP1B restricts its accumulation to a single neurite tip, and mTOR counteracts this degradation to permit axon specification (PMID:17318188, PMID:18842593). RAP1B also acts as a conditional oncoprotein in thyroid tissue, where constitutively active RAP1B drives follicular thyroid carcinogenesis downstream of PKA, and genetic deletion of Rap1b suppresses PKA-driven thyroid tumors in vivo (PMID:15331589, PMID:29882482).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 High

    Establishing RAP1B as a PKA substrate in platelets resolved how cAMP signaling directly modifies a Ras-family GTPase, identifying Ser179 in the C-terminal region as the key phosphorylation site and showing activation-dependent redistribution from membrane to cytoskeleton.

    Evidence Protein purification, peptide sequencing, and 32P-labeling in intact platelets; subcellular fractionation after thrombin/ionophore activation

    PMID:1696481 PMID:2123187

    Open questions at the time
    • Functional consequence of Ser179 phosphorylation on GTPase cycle unknown
    • Cytoskeletal association mechanism not defined
  2. 1993 High

    Mutagenesis pinpointed Ser179 as the sole PKA phosphorylation site and revealed that PKG also phosphorylates this residue, establishing convergent inhibitory regulation by both cyclic nucleotide kinases.

    Evidence Site-directed mutagenesis with S179K substitution, in vitro PKG kinase assay with phosphoamino acid analysis

    PMID:1551424 PMID:1901412 PMID:8463283

    Open questions at the time
    • Structural mechanism of how Ser179 phosphorylation alters function unknown
    • In vivo significance of PKG phosphorylation untested
  3. 1995 High

    Demonstration that cAMP-elevating agents increase RAP1B GTP loading in cells established agonist-dependent activation and opened the question of which GEFs mediate this response.

    Evidence GTP/GDP ratio measurement by TLC after 32P-orthophosphate labeling in cAMP-stimulated cells

    PMID:7737967

    Open questions at the time
    • Identity of the cAMP-responsive GEF not yet determined
    • Cell-type specificity of activation not explored
  4. 1996 High

    The finding that GTP-bound, prenylated RAP1B directly stimulates B-Raf kinase activity to phosphorylate MEK identified the first effector pathway and linked RAP1B to MAPK signaling.

    Evidence Reconstituted cell-free B-Raf kinase assay with nucleotide-loaded, lipid-modified recombinant RAP1B

    PMID:8576107

    Open questions at the time
    • In vivo relevance of RAP1B–B-Raf axis not demonstrated
    • Tissue/context specificity unknown
  5. 2002 High

    Multiple studies converged to establish RAP1B as the central GTPase for integrin αIIbβ3 inside-out activation in megakaryocytes/platelets and delineated two upstream pathways: Gαi/PI3K(PtdIns(3,4,5)P3) and Gαq/Ca²⁺.

    Evidence Viral transduction of active/dominant-negative RAP1B in megakaryocytes; Gαz, Gαi2, Gαq, PI3Kγ KO mouse platelets with pharmacological PI3K inhibitors; exogenous PIP3 addition

    PMID:11970953 PMID:11994301 PMID:12407113

    Open questions at the time
    • In vivo hemostatic consequence of RAP1B loss not yet shown
    • GEF identity in platelets not resolved
  6. 2004 High

    RAP1B localization to a single neurite tip was shown to be the decisive event in axon specification, acting upstream of Cdc42/Par complex, while constitutively active RAP1B in vivo caused thyroid tumors, revealing context-dependent oncogenic potential.

    Evidence RNAi, dominant-active/dominant-negative mutants, and live imaging in hippocampal neurons; conditional transgenic mouse with thyroid-specific G12V-RAP1B

    PMID:15286792 PMID:15331589

    Open questions at the time
    • Mechanism restricting RAP1B to one neurite unknown
    • Whether thyroid oncogenesis requires specific effectors not tested
  7. 2005 High

    Rap1b knockout mice provided definitive genetic evidence that RAP1B is required for platelet integrin activation, aggregation, and normal hemostasis in vivo.

    Evidence Rap1b−/− mouse with platelet aggregation, integrin activation, tail-bleeding, and arterial thrombosis assays

    PMID:15696195

    Open questions at the time
    • Contribution of secretion defects versus integrin defects not separated
    • Redundancy with Rap1a not fully addressed
  8. 2007 High

    Identification of Smurf2 as the E3 ubiquitin ligase that degrades inactive RAP1B explained how spatial restriction to one neurite is achieved, providing the degradation-based polarity mechanism.

    Evidence Ubiquitination assays, proteasome inhibition, and RNAi epistasis in hippocampal neurons

    PMID:17318188

    Open questions at the time
    • Degron/ubiquitination site on RAP1B not mapped
    • How Smurf2 distinguishes GDP- from GTP-bound RAP1B unclear
  9. 2008 High

    The crystal structure of the Epac2–cAMP–RAP1B complex revealed the conformational switch mechanism by which cAMP binding to Epac2 relieves autoinhibition and traps RAP1B during nucleotide exchange, while mTOR/Rheb were placed upstream of RAP1B stabilization in neurons.

    Evidence X-ray crystallography/single-particle EM of Epac2–RAP1B complex; Rheb/mTOR/Smurf2 epistasis with rapamycin in hippocampal neurons

    PMID:18660803 PMID:18842593

    Open questions at the time
    • Whether Epac1 engages RAP1B identically not structurally resolved
    • mTOR mechanism of Smurf2 antagonism unclear
  10. 2008 High

    RAP1B knockout revealed essential roles in NK-cell IQGAP1/B-Raf/C-Raf/ERK signalosome formation and B-cell adhesion, homing, and humoral immunity, extending RAP1B function beyond platelets into adaptive and innate immunity.

    Evidence Rap1b KO mice with co-IP, confocal colocalization, B-cell enumeration, in vivo homing, and immunization

    PMID:18714009 PMID:20733035

    Open questions at the time
    • Whether IQGAP1 binding is direct or via B-Raf not determined
    • Relative Rap1a versus Rap1b contributions in B cells not resolved
  11. 2009 High

    Hydrogen/deuterium exchange mass spectrometry revealed that PKA phosphorylation at Ser179 allosterically remodels switch I and switch II loops far from the modification site, providing a structural basis for how phosphorylation inhibits effector engagement.

    Evidence DXMS of phosphorylated versus unphosphorylated RAP1B; S179D phosphomimetic validation

    PMID:19651783

    Open questions at the time
    • Effect on specific effector binding (talin, B-Raf) not directly tested
    • Full atomic-resolution structure of phospho-RAP1B unavailable
  12. 2013 High

    Two independent studies established that PKA phosphorylates CalDAG-GEFI (Ser116/Ser586), and this is the primary mechanism by which cAMP/PKA inhibits RAP1B activation in platelets—resolving a longstanding question of whether PKA acts on RAP1B directly or via its GEF.

    Evidence Mass spectrometry of CalDAG-GEFI phosphosites, phosphomimetic/alanine mutants, Rap1B-GTP pulldown in HEK293 cells and platelets

    PMID:23600630 PMID:23611601

    Open questions at the time
    • Relative contributions of direct RAP1B Ser179 phosphorylation versus CalDAG-GEFI inhibition in vivo not quantified
  13. 2013 High

    FRET biosensor imaging localized active RAP1B specifically to the longest neurite tip and effector mutant analysis dissected two downstream polarity pathways: RalA/Nore1A and PI3K.

    Evidence Live FRET imaging plus effector domain mutants (G12V/E37G, G12V/Y40C) and Nore1A RNAi in hippocampal neurons

    PMID:24165023

    Open questions at the time
    • How RalA/Nore1A and PI3K pathways converge on polarity machinery unclear
    • Whether both pathways are required simultaneously not determined
  14. 2014 High

    RAP1B was shown to maintain vascular tone and blood pressure through NO-dependent vasodilation and myosin phosphatase regulation, while in neutrophils RAP1B restrains PI3K-Akt signaling and transcellular diapedesis.

    Evidence Rap1b KO mice with blood pressure telemetry, ex vivo vessel assays, myosin phosphatase phosphorylation; Rap1b KO neutrophil transendothelial migration and in vivo Akt inhibition

    PMID:24790136 PMID:25092872

    Open questions at the time
    • Direct molecular target of RAP1B in smooth muscle relaxation not identified
    • Whether SHP-1 is a direct RAP1B effector in neutrophils requires validation
  15. 2016 Medium

    PKA phosphorylation of RAP1B (but not RAP1A) was shown to specifically disrupt SmgGDS-607 binding and block prenylation, revealing an isoform-specific mechanism by which phosphorylation controls RAP1B membrane targeting, while a C3G/Crkl/VASP complex was identified as a platelet GEF pathway for RAP1B.

    Evidence Co-IP of SmgGDS-607 with RAP1B/RAP1A, metabolic prenylation assay, mutagenesis; GST-Crkl pull-down with VASP, VASP KO platelet Rap1b-GTP pulldown

    PMID:27620165 PMID:27760305

    Open questions at the time
    • Whether SmgGDS-607 loss fully accounts for membrane targeting defect not tested in vivo
    • How C3G/Crkl/VASP and CalDAG-GEFI pathways integrate not resolved
  16. 2017 High

    The crystal structure of RAP1B–talin-F0 revealed the structural basis for effector-like talin recruitment to membranes, directly linking RAP1B GTP loading to integrin activation via inside-out signaling.

    Evidence X-ray crystallography of RAP1B–talin-F0 complex, vesicle reconstitution, mutagenesis, cell adhesion/spreading assays

    PMID:29170462

    Open questions at the time
    • Whether this mechanism operates identically for all integrin subtypes unknown
    • In vivo contribution of talin-F0–RAP1B interaction to hemostasis not tested
  17. 2018 High

    Endothelial-specific conditional knockouts demonstrated that RAP1B is the primary isoform required for VEGF-induced barrier dissolution, while compound Rap1b/Prkar1a KO established RAP1B as the obligate downstream effector of PKA-driven thyroid carcinogenesis.

    Evidence EC-specific Rap1a/Rap1b conditional KO mice with Miles assay and ECIS; compound Prkar1a/Rap1b conditional KO mouse thyroid tumor incidence

    PMID:29222111 PMID:29882482

    Open questions at the time
    • Mechanism by which RAP1B opens endothelial junctions not molecularly defined
    • RAP1B effectors in thyroid oncogenesis not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how Smurf2 selectively recognizes GDP-bound RAP1B for ubiquitination, the identity of the ubiquitination site(s), how RAP1B differentially engages its many effectors in a tissue-specific manner, and the atomic-resolution structural basis for phospho-Ser179-dependent inhibition of effector binding.
  • Smurf2 recognition determinant on RAP1B unknown
  • Full phospho-RAP1B crystal structure unavailable
  • Tissue-specific effector selectivity mechanism unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 6 R-HSA-109582 Hemostasis 5 R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1643685 Disease 3
Partners
BRAFIQGAP1RAPGEF3RAPGEF4RASGRP2SMGGDSSMURF2TLN1
Complex memberships
C3G/Crkl/VASP GEF complexIQGAP1/B-Raf/C-Raf signalosome

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Crystal structure of Epac2 in complex with a cAMP analogue and RAP1B determined by X-ray crystallography and single particle electron microscopy, revealing that cAMP binding causes conformational changes in Epac2 that swing the cyclic nucleotide binding domain from a position blocking the Rap binding site to a docking site at the Ras exchange motif domain, trapping RAP1B in the course of the exchange reaction. X-ray crystallography, single particle electron microscopy Nature High 18660803
2017 Structural determination of Rap1b bound to talin-F0 domain revealed that talin-F0 binds Rap1b like canonical Rap1 effectors despite little sequence homology; disruption of the binding strongly impairs integrin activation, cell adhesion, and cell spreading. The Rap1b/talin interaction becomes strong upon attachment of activated Rap1b to vesicular membranes, identifying a membrane-targeting mechanism for talin to activate integrin. X-ray crystallography, vesicle reconstitution, mutagenesis, cell adhesion assays Nature communications High 29170462
2015 Crystal structure of Rap1B bound to a non-hydrolyzable GTP analog solved, revealing that Rap1B crystallizes in an intermediate state distinct from H-Ras and Rap2A, and that residues distant from the nucleotide control how readily the protein adopts the fully activated conformation. X-ray crystallography, mutagenesis Biochemical and biophysical research communications High 25935485
2004 Localization of the GTPase Rap1B to the tip of a single neurite is a decisive step in determining which neurite becomes the axon in rat hippocampal neurons; Rap1B acts upstream of Cdc42 and the Par complex (Par3/Par6/aPKC) to initiate axon development. RNA interference, dominant-active/dominant-negative GTPase mutants, live imaging, epistasis analysis in cultured hippocampal neurons Nature neuroscience High 15286792
2005 Genetic knockout of Rap1b in mice causes defective platelet aggregation and reduced activation of integrin αIIbβ3 in response to both GPCR-linked and GPCR-independent agonists, demonstrating that Rap1b is required for a common integrin inside-out activation pathway and normal hemostasis in vivo. Rap1b knockout mouse, platelet aggregation assays, integrin activation assays, tail bleeding time, arterial thrombosis model The Journal of clinical investigation High 15696195
2007 The ubiquitin E3 ligase Smurf2 ubiquitinates inactive Rap1B and initiates its proteasomal degradation, restricting Rap1B to a single neurite and thereby ensuring neuronal polarity with a single axon; Smurf1 regulates Rho in a parallel pathway controlling neurite growth. RNAi knockdown, ubiquitination assays, proteasome inhibition, epistasis in hippocampal neurons The EMBO journal High 17318188
1990 Rap1B (not Rap1A) is the substrate phosphorylated by cAMP-dependent protein kinase A in intact human platelets; phosphorylation occurs on a serine residue at the C-terminal region, identified by sequencing of proteolytic peptides from the purified phosphoprotein. Protein purification, proteolytic peptide sequencing, kinetic comparison of synthetic peptides, 32P-labeling of intact platelets Biochemical and biophysical research communications High 1696481
1993 Mutational analysis identified Ser179 as the residue phosphorylated by cAMP-dependent protein kinase A in Rap1b; substitution of Ser179 with Lys (resembling Rap1a) renders Ser180 a substrate for PKA. Site-directed mutagenesis, transient expression, 32P-labeling, SDS-PAGE mobility shift The Journal of biological chemistry High 8463283
1992 Rap1B (smg p21B) is phosphorylated by cyclic GMP-dependent protein kinase (PKG) on the same Ser179 residue as PKA in a cell-free system. In vitro kinase assay, phosphoamino acid analysis FEBS letters High 1551424
1991 Neuronal CaM kinase Gr phosphorylates Rap1b selectively on a serine residue near the C-terminus (same or contiguous to the PKA site) in a Ca2+/calmodulin-dependent manner; other Ras family members (Rab-3A, Rap-2b, Ha-ras p21) are not substrates. In vitro kinase assay with purified CaM kinase Gr and recombinant Rap-1b, phosphoamino acid analysis, substrate specificity panel Proceedings of the National Academy of Sciences of the United States of America High 1901412
1996 GTP-bound Rap1B directly stimulates B-Raf protein kinase activity to phosphorylate MEK in a cell-free assay; the GTP-bound and fully lipid-modified (prenylated) form is required for activity; maximum B-Raf activation is comparable to that induced by Ki-Ras, and Rap1B enhances Ki-Ras-stimulated B-Raf activity additively. Cell-free B-Raf kinase assay, immunoprecipitated B-Raf, recombinant Rap1B with defined nucleotide loading, in vitro MEK phosphorylation The Journal of biological chemistry High 8576107
1995 Treatment of cells with cAMP-elevating agents results in activation of Rap1b (increased GTP/GDP ratio), demonstrating agonist-dependent activation of Rap1 proteins for the first time. GTP/GDP ratio measurement by thin-layer chromatography following [32P]-orthophosphate labeling, pharmacological cAMP elevation The Journal of biological chemistry High 7737967
2009 PKA-mediated phosphorylation of Rap1b on Ser179 induces allosteric conformational changes in the two switch loops (switch I and switch II) that are distal from the phosphorylation site, as revealed by amide hydrogen/deuterium exchange mass spectrometry; the phosphomimetic S179D mutant recapitulates the same changes. Hydrogen/deuterium exchange mass spectrometry (DXMS), phosphomimetic mutant analysis The Journal of biological chemistry High 19651783
2002 Constitutively active Rap1b (V12) augments agonist-induced fibrinogen binding to integrin αIIbβ3 in megakaryocytes through effects on integrin affinity (inside-out signaling); dominant-negative Rap1b (N17) or Rap1GAP expression inhibit agonist-induced fibrinogen binding. The Rap1b effect requires actin polymerization and is cell-autonomous. Viral transduction of GFP-Rap1b mutants into megakaryocytes, fibrinogen binding assay with FAB fragment POW-2, cytochalasin D/latrunculin A treatment The Journal of biological chemistry High 11994301
1990 In resting platelets, Rap1b is membrane-associated; upon activation with thrombin or calcium ionophore A23187, Rap1b quantitatively redistributes to associate with the actin cytoskeleton (10,000×g fraction), a process regulated by cell activation. Subcellular fractionation (Triton X-100 lysis, differential centrifugation), immunoblotting The Journal of biological chemistry High 2123187
1994 Both Rap1A and Rap1B proteins localize to late endocytic compartments (late endosomes/lysosomes) in fibroblasts and to phagosomes with late endocytic biochemical features in J774 macrophages, as determined by confocal immunofluorescence and subcellular fractionation. Confocal immunofluorescence with affinity-purified antibodies, subcellular fractionation, vaccinia T7 overexpression system Journal of cell science High 7962206
2002 Rap1b activation in platelets is stimulated by Gαi family members (Gαz and Gαi2) via a PI3Kγ-dependent mechanism; Gαq-coupled pathways contribute to ADP-stimulated Rap1 activation via Ca2+-dependent mechanisms. Gi-mediated Rap1 activation does not involve enhanced intracellular calcium release. Gαz KO, Gαi2 KO, Gαq KO mouse platelets; PI3Kγ KO mice; PI3K inhibitors (wortmannin, LY294002); ADP receptor-selective inhibitors; [32P]-GTP binding assay The Journal of biological chemistry High 11970953
2002 Gi-dependent activation of Rap1B in platelets requires PI3K-generated PtdIns(3,4,5)P3 specifically (not PtdIns(3,4)P2); a PI3K isoform distinct from PI3Kγ mediates this effect downstream of ADP and epinephrine. PI3K inhibitors (wortmannin, LY294002), PI3Kγ-KO mouse platelets, exogenous lipid addition (PtdIns(3,4,5)P3 vs PtdIns(3,4)P2), Rap1B-GTP pulldown assay The Journal of biological chemistry High 12407113
2002 cAMP inhibits Akt activity in thyroid follicular cells via a mechanism requiring both activation and PKA-mediated phosphorylation of Rap1b; dominant-negative or non-phosphorylatable Rap1b blocks the cAMP-mediated inhibition of Akt. Dominant-negative Rap1b expression, PKA inhibitors, Akt kinase activity assay in PCCL3 thyroid cells The Journal of biological chemistry Medium 12089143
2002 cAMP-dependent G1/S phase entry in thyroid follicular cells requires both activation (GTP loading) and phosphorylation of Rap1b by PKA; PKA-phosphorylation–deficient Rap1b fails to support cAMP-induced DNA synthesis. Expression of phosphorylation-deficient Rap1b mutants, BrdU incorporation, dominant-negative constructs, PKA inhibitors Proceedings of the National Academy of Sciences of the United States of America Medium 11959997
1998 Expression of Rap1b in thyroid follicular cells (where cAMP is mitogenic) decreases cell doubling time, increases saturation density, and causes anchorage-dependent transformation and tumor formation in nude mice, demonstrating that Rap1b can act as a conditional oncoprotein. Stable Rap1b overexpression, growth curve analysis, nude mouse xenograft Proceedings of the National Academy of Sciences of the United States of America Medium 9636174
2004 Constitutively active G12V-Rap1b expression in thyroid tissue in vivo (using a conditional transgenic mouse model) causes thyroid tumor formation, providing genetic evidence for Rap1b's oncogenic action in vivo. Conditional transgenic mouse (Cre/loxP), thyroid-specific G12V-Rap1b expression, histopathology The Journal of biological chemistry High 15331589
2008 Rap1b regulates natural killer cell signaling by colocalizing with scaffolding protein IQGAP1 upon activation, facilitating sequential phosphorylation of B-Raf, C-Raf, and ERK1/2 and formation of a signalosome in the perinuclear region; Rap1b deficiency impairs LFA1 polarization, MTOC formation, and NKG2D/Ly49D/NCR1-mediated cytokine production. Rap1b KO mice, confocal colocalization, co-immunoprecipitation, phospho-Western blotting, MTOC/spreading assays The Journal of experimental medicine High 20733035
2011 Agonist-induced Rap1b activation stimulates platelet granule secretion (ATP secretion, P-selectin expression); additionally, integrin αIIbβ3 outside-in signaling (platelet spreading on fibrinogen, clot retraction) activates Rap1b via Src kinase, PKC, and calcium-dependent mechanisms, distinct from inside-out activation pathways. Rap1b KO mouse platelets, ATP secretion assay, P-selectin expression, clot retraction, spreading on fibrinogen, selective pharmacological inhibitors (PP2, Ro-31-8220, BAPTA/AM) The Journal of biological chemistry High 21940635
2013 Adenosine A2B receptor activation phosphorylates Rap1B (via PKA), which decreases Rap1B interaction with the chaperone SmgGDS, suppresses Rap1B prenylation, promotes cytosolic/nuclear accumulation of non-prenylated Rap1B, diminishes cell-cell adhesion, and causes cell scattering. Co-immunoprecipitation of Rap1B with SmgGDS, metabolic prenylation labeling, pharmacological A2B receptor activation/inhibition, PKA inhibitors, cellular fractionation Science signaling High 23716716
2015 β-adrenergic receptor activation (via Gαs/PKA) phosphorylates Rap1B on Ser179/180, inhibits its prenylation and membrane localization, reduces cell-cell adhesion, and promotes breast cancer cell scattering and migration; propranolol (β-blocker) reverses these effects. β-AR agonist treatment, cholera toxin, PKA pathway manipulation, prenylation assay (metabolic labeling), membrane fractionation, cell-cell adhesion and migration assays Cancer biology & therapy Medium 26209110
2016 PKA phosphorylation of Rap1B specifically inhibits its prenylation and binding to SmgGDS-607; phosphorylation in the polybasic region (PBR) of Rap1B (Ser179/180) inhibits SmgGDS-607 binding, whereas the analogous phosphorylation in Rap1A's PBR does not inhibit SmgGDS-607 binding or prenylation, revealing isoform-specific regulatory differences. Co-immunoprecipitation, homology modeling, metabolic prenylation assay, mutagenesis of SmgGDS-607 binding residues, GPCR activation Journal of molecular biology Medium 27760305
2013 CalDAG-GEFI (calcium and diacylglycerol-regulated GEF) is phosphorylated by PKA on Ser116 and Ser586 in platelets; phosphorylation at Ser587 (equivalent to Ser586) prevents CalDAG-GEFI from activating Rap1b in response to Ca2+, identifying phosphorylation of CalDAG-GEFI as the primary mechanism by which cAMP/PKA inhibits Rap1b in platelets. Radioactive phosphate incorporation, mass spectrometry, phospho-specific antibody, Rap1-GTP pulldown assay, phosphomimetic and alanine mutants in HEK293 cells and platelets Journal of thrombosis and haemostasis High 23611601
2013 CalDAG-GEFI is phosphorylated by PKA on Ser116 and Ser586 in intact platelets and in vitro; phosphorylation prevents CalDAG-GEFI-mediated Rap1b activation induced by Ca2+ ionophore, and mutation of both sites abolishes PKA inhibitory effect on Rap1b. In vitro PKA phosphorylation of recombinant CalDAG-GEFI, forskolin treatment of platelets, phospho-specific antibodies, mutant CalDAG-GEFI transfection in HEK293 cells, Rap1b-GTP pulldown The Biochemical journal High 23600630
2008 Rheb and mTOR regulate axon specification through Rap1B; PI3K activates Rheb→mTOR, which counteracts Smurf2-initiated proteasomal degradation of Rap1B to maintain sufficient Rap1B levels for axon formation. Suppression of Smurf2 rescues axon formation lost by Rheb knockdown. RNAi (Rheb, mTOR, Smurf2), rapamycin treatment, dominant-negative 4E-BP1 mutants, Rap1B protein level measurement, epistasis in hippocampal neurons The Journal of biological chemistry High 18842593
2008 Rap1b deficiency in mice impairs B-Raf→C-Raf→ERK signaling in NK cells via failure to form the IQGAP1 signalosome; Rap1b is required for B cell development (pro/pre-B cell numbers), marginal zone B cell homeostasis, B cell adhesion to stromal cells, chemokine-directed migration (SDF-1, CXCL13), lymph node homing, and T-dependent humoral immunity. Rap1b KO mouse, B cell enumeration, in vitro adhesion and migration assays, in vivo homing, T-dependent/T-independent immunization Journal of immunology High 18714009
1992 Rap1B forms a complex with rasGAP and phospholipase C-γ1 in human platelets; thrombin stimulation induces the association of Rap1B with rasGAP, suggesting formation of a multi-protein signaling complex. Co-immunoprecipitation with anti-rasGAP antibodies, Western blotting, PLC-γ1 activity measurement Proceedings of the National Academy of Sciences of the United States of America Medium 1323853
1992 Epinephrine via the α2-adrenergic receptor specifically suppresses Rap1B.GAP-activated GTPase activity in human platelet lysates, with no effect on ras.GAP or rap2B.GAP activity; the effect is blocked by the α2-antagonist yohimbine. In vitro GTPase assay with platelet lysates, pharmacological agonist/antagonist treatment, anion-exchange chromatography Proceedings of the National Academy of Sciences of the United States of America Medium 1313568
1999 Von Willebrand factor stimulation causes translocation of Rap1B (and Rap2B) to the platelet cytoskeleton via FcγRII receptor-mediated protein tyrosine phosphorylation; translocation of Rap1B is prevented by cytochalasin D, anti-FcγRII antibody, tyrosine kinase inhibitor genistein, or cAMP-increasing agents. Subcellular fractionation, Western blotting, neutralizing antibodies, pharmacological inhibitors (genistein, cytochalasin D), anti-GPIb antibody The Journal of biological chemistry Medium 10224142
2002 High glucose activates Rap1b in renal mesangial cells via a PKC-dependent (PDGF-independent) pathway, and activated Rap1b stimulates B-Raf (but not Raf-1) to increase fibronectin synthesis; dominant-negative Rap1b mutants (S17N, T61R) block high glucose-induced fibronectin expression. Transfection of Rap1b and dominant-negative mutants, B-Raf/Raf-1 Western blotting, fibronectin mRNA/protein measurement, PKC inhibitors, Rap1b-GTP activation assay The Journal of biological chemistry Medium 12196513
2008 Rap1b protects against high glucose-induced mitochondrial dysfunction and apoptosis in renal tubular cells; Rap1b physically interacts with Bcl-2 via Bcl-2's BH4 domain, and this interaction is disrupted by high glucose; overexpression of Rap1b partially restores Bcl-2/Bax balance and mitochondrial function. Co-immunoprecipitation (Bcl-2/Rap1b interaction), BH4 domain deletion mutants, Rap1b overexpression, mitochondrial morphology, DNA fragmentation assay, GTPase activity assay Journal of the American Society of Nephrology Medium 18753253
2014 Rap1b deficiency in neutrophils enhances PI3K-Akt activation and promotes transcellular diapedesis through endothelial cells via invadopodia-like protrusions; in vivo Akt inhibition suppresses excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. Rap1b's inhibitory action on PI3K signaling may be mediated by activation of phosphatase SHP-1. Rap1b KO mice, in vitro transendothelial migration assay, PI3K/Akt inhibition, Akt phosphorylation Western blot, SHP-1 phosphatase assay, LPS-induced lung injury model The Journal of experimental medicine High 25092872
2014 Rap1b in smooth muscle and endothelium is required for maintenance of vascular tone and normal blood pressure; Rap1b-deficient vessels show increased contractility, inhibitory phosphorylation of myosin phosphatase under basal conditions, decreased cAMP/Epac-dependent relaxation, and impaired nitric oxide-dependent vasodilation. Rap1b KO mouse, blood pressure telemetry, ex vivo vessel contraction/dilation assays, losartan rescue experiment, myosin phosphatase phosphorylation Western blot, NO-dependent vasodilation assay Arteriosclerosis, thrombosis, and vascular biology High 24790136
2015 EPAC (exchange protein directly activated by cAMP) activates Rap1b to regulate neuronal polarity; pharmacological EPAC activation induces supernumerary axons in rat hippocampal neurons, an effect dependent on Rap1b; EPAC1 knockdown or knockout impairs axon elongation and polarization. EPAC pharmacological activator (8-pCPT), shRNA knockdown, EPAC1 KO mouse neurons, axon marker analysis (ankyrin G, synaptophysin, vGLUT1), dominant-active Rap1b The Journal of neuroscience High 26269639
2013 FRET imaging in hippocampal neurons demonstrates that Rap1B activity is specifically elevated at the tip of the future axon (longest neurite). Effector mutant analysis shows that Rap1B promotes neuronal polarization via at least two pathways: RalA/Nore1A (via the Ral/Raf-like effector domain) and PI3-kinase. FRET-based Rap1B activity biosensor (live imaging), Rap1B effector mutants (G12V/E37G for Ral/Nore, G12V/Y40C for PI3K), dominant-negative RalA, Nore1A RNAi Genes to cells High 24165023
2003 GTP-bound (active) Rap1B translocates to the nucleus in squamous carcinoma cells, whereas GDP-bound (inactive) Rap1B is retained in the cytoplasm/perinuclear region; growth factors induce nuclear translocation of Rap1. GFP-tagged constitutively active (G12V) and dominant-negative Rap1B transfection, confocal microscopy, subcellular fractionation, immunohistochemistry of human oral cancer specimens Oncogene Medium 13679863
2008 Both Rap1a and Rap1b are required for endothelial cell functions including adhesion to extracellular matrices, cell migration, monolayer integrity, three-dimensional tube formation, and FGF2-induced ERK, p38, and Rac activation in human microvascular endothelial cells. siRNA knockdown of rap1a or rap1b in HMVECs, adhesion assay, migration assay, Matrigel tube formation, aortic ring sprouting assay, rap1a KO mouse Matrigel plug angiogenesis, ERK/p38/Rac activation Western blot Molecular and cellular biology High 18625726
2011 Rap1A (not Rap1B) is the predominant isoform controlling endothelial junction formation and barrier integrity; Rap1A has greater junctional localization and stronger association with AF-6/afadin than Rap1B. Knockdown of Rap1A increases VE-cadherin gaps, while Rap1B knockdown does not. miRNA-based isoform-specific knockdown, electrical impedance sensing, VE-cadherin immunostaining, GFP-Rap1A/B localization quantification, co-immunoprecipitation of AF-6 Small GTPases Medium 21776404
2018 Rap1B (not Rap1A) is the primary isoform essential for VEGF-induced endothelial barrier dissolution and AJ remodeling in vitro; both Rap1A and Rap1B are required for de novo AJ formation and recovery from LPS-induced barrier disruption in vivo. EC-specific Rap1A and Rap1B conditional KO mice, in vivo vascular permeability assay (Miles assay), monolayer resistivity (ECIS), VE-cadherin junction imaging, STZ-induced diabetes model Journal of cell science High 29222111
2017 RAP1B interacts with DVL2 (a Wnt pathway regulator) and activates β-catenin/TCF signaling in esophageal squamous cell carcinoma cells; gain/loss-of-function experiments show RAP1B promotes ESCC cell growth, migration, and metastasis. Co-immunoprecipitation of RAP1B with DVL2, TCF reporter assay (luciferase), RAP1B overexpression and siRNA knockdown, invasion/migration assays Gene Medium 28119087
2017 Rap1b acts downstream of Axin2 as a signaling effector integrating BMP and FGF signals during skeletal development; BMP signaling activates Rap1b via Axin2, and Rap1b promotes chondrogenesis while inhibiting MAPK to repress osteoblast differentiation. Rap1b KO mice display severe craniofacial and body skeletal defects. Rap1b KO mouse genetic analysis, conditional Axin2 KO, BMP treatment, MAPK/ERK activation Western blot, chondrogenic and osteogenic differentiation assays Journal of bone and mineral research Medium 28520221
2016 VASP forms a complex with Crkl (an adaptor protein for the Rap1b GEF C3G) in platelets; PKA-mediated phosphorylation of VASP on Ser157 abrogates VASP-Crkl binding. Loss of VASP reduces agonist-induced Rap1b activation, demonstrating that a C3G/Crkl/VASP complex promotes Rap1b activation. Co-immunoprecipitation of Crkl and VASP from platelet lysates, GST-Crkl domain pull-down with recombinant VASP, confocal colocalization, VASP KO mouse platelets, Rap1b-GTP pulldown assay Cell communication and signaling Medium 27620165
2019 In zebrafish, Rap1b stimulates integrin β1 to enhance adhesion of posterior lateral plate mesoderm cells to fibronectin at somite boundaries, facilitating their spreading and physical contact with Notch-ligand-expressing somitic cells to promote Notch-mediated hemogenic endothelium specification and HSC development. Zebrafish rap1b morpholino knockdown, integrin β1 blocking, fibronectin matrix imaging, Notch reporter assay, epistasis with Notch pathway Developmental cell Medium 31006651
2013 Rap1b knockdown in zebrafish, in the context of integrin α5 mutation, abolishes fibronectin matrix assembly and somite border morphogenesis, placing Rap1b upstream of integrin α5 activation in an inside-out signaling pathway that promotes integrin-fibronectin binding and FN matrix assembly. Rap1b morpholino knockdown, integrin α5 mutant zebrafish, dominant-negative Rap1b, FN matrix immunostaining, her1 oscillation analysis Developmental dynamics Medium 23192979
2009 Isoproterenol suppresses LPA-induced glioma cell migration via β2-adrenergic receptor/cAMP/Epac/Rap1B/inhibition of Rac signaling; PTEN expression is required for Rap1B-mediated inhibition of Rac1 and Akt. siRNA knockdown of Rap1B and PTEN, dominant-negative Rap1B, pharmacological EPAC activator, Rac1 GTP pulldown, Akt phosphorylation assay, migration assay Molecular biology of the cell Medium 19864456
2018 Deletion of Rap1b (but not Rap1a or Epac1) in the context of Prkar1a KO (PKA activation) significantly decreases thyroid size and follicular thyroid cancer incidence, establishing Rap1b as the downstream effector of PKA-driven thyroid carcinogenesis in vivo. Compound Prkar1a/Rap1b conditional KO mouse, histopathology, thyroid tumor incidence Thyroid High 29882482
2022 Loss of Rap1b in neutrophils increases Ldha (lactate dehydrogenase A) activity, elevating intracellular acidity, which drives formation of invasive-like protrusions and transcellular migration through endothelial cells; Ldha inhibition in vivo limits pathogenic neutrophil tissue infiltration and vascular leakage. Rap1b KO mouse, proteomics, Ldha activity assay, pH measurement, Ldha inhibitor in vivo, transcellular vs paracellular migration imaging, vascular leakage assay, ischemia/reperfusion model Frontiers in immunology Medium 36505495

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Nature neuroscience 316 15286792
2005 Rap1b is required for normal platelet function and hemostasis in mice. The Journal of clinical investigation 254 15696195
2002 Activation of Rap1B by G(i) family members in platelets. The Journal of biological chemistry 156 11970953
2002 Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeleton. The Journal of biological chemistry 155 11994301
2008 Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B. Nature 154 18660803
1994 Association of Rap1a and Rap1b proteins with late endocytic/phagocytic compartments and Rap2a with the Golgi complex. Journal of cell science 148 7962206
1996 Activation of brain B-Raf protein kinase by Rap1B small GTP-binding protein. The Journal of biological chemistry 136 8576107
1998 Mitogenic and oncogenic properties of the small G protein Rap1b. Proceedings of the National Academy of Sciences of the United States of America 124 9636174
1995 Cyclic AMP-dependent activation of Rap1b. The Journal of biological chemistry 118 7737967
2002 A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets. The Journal of biological chemistry 105 11815620
2015 Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B. Nature communications 95 25569036
2008 Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions. Molecular and cellular biology 89 18625726
2002 A selective role for phosphatidylinositol 3,4,5-trisphosphate in the Gi-dependent activation of platelet Rap1B. The Journal of biological chemistry 83 12407113
2017 Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nature communications 82 29170462
2013 An adenosine-mediated signaling pathway suppresses prenylation of the GTPase Rap1B and promotes cell scattering. Science signaling 80 23716716
1990 Rap1-B is phosphorylated by protein kinase A in intact human platelets. Biochemical and biophysical research communications 77 1696481
1990 rap1B, a cAMP-dependent protein kinase substrate, associates with the platelet cytoskeleton. The Journal of biological chemistry 76 2123187
2007 Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. The EMBO journal 74 17318188
2008 Rap1b GTPase ameliorates glucose-induced mitochondrial dysfunction. Journal of the American Society of Nephrology : JASN 70 18753253
2002 cAMP inhibition of Akt is mediated by activated and phosphorylated Rap1b. The Journal of biological chemistry 70 12089143
2003 Rap1A and rap1B ras-family proteins are prominently expressed in the nucleus of squamous carcinomas: nuclear translocation of GTP-bound active form. Oncogene 67 13679863
2005 The small GTPase Rap1b regulates the cross talk between platelet integrin alpha2beta1 and integrin alphaIIbbeta3. Blood 66 16357324
2017 Long non-coding RNA MALAT1 promotes proliferation and suppresses apoptosis of glioma cells through derepressing Rap1B by sponging miR-101. Journal of neuro-oncology 64 28551849
2022 Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway. Journal of hazardous materials 63 36029734
2011 Isoform-specific differences between Rap1A and Rap1B GTPases in the formation of endothelial cell junctions. Small GTPases 63 21776404
1992 Role of rap1B and p21ras GTPase-activating protein in the regulation of phospholipase C-gamma 1 in human platelets. Proceedings of the National Academy of Sciences of the United States of America 63 1323853
2012 Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation. The international journal of biochemistry & cell biology 62 22642900
2002 On the mitogenic properties of Rap1b: cAMP-induced G(1)/S entry requires activated and phosphorylated Rap1b. Proceedings of the National Academy of Sciences of the United States of America 62 11959997
1991 Phosphorylation of a Ras-related GTP-binding protein, Rap-1b, by a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr. Proceedings of the National Academy of Sciences of the United States of America 62 1901412
2011 Distinct roles for Rap1b protein in platelet secretion and integrin αIIbβ3 outside-in signaling. The Journal of biological chemistry 61 21940635
2008 Rheb and mTOR regulate neuronal polarity through Rap1B. The Journal of biological chemistry 59 18842593
2016 miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B. Oncotarget 58 27729617
1993 Mutational analysis of the cAMP-dependent protein kinase-mediated phosphorylation site of Rap1b. The Journal of biological chemistry 58 8463283
2012 miR-518b is down-regulated, and involved in cell proliferation and invasion by targeting Rap1b in esophageal squamous cell carcinoma. FEBS letters 56 22958893
2014 miR-128 and miR-149 enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeletal remodeling in glioblastoma. Oncology reports 53 25017996
2008 Rap1b regulates B cell development, homing, and T cell-dependent humoral immunity. Journal of immunology (Baltimore, Md. : 1950) 51 18714009
2014 Rap1b in smooth muscle and endothelium is required for maintenance of vascular tone and normal blood pressure. Arteriosclerosis, thrombosis, and vascular biology 49 24790136
2014 The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. The Journal of experimental medicine 48 25092872
1999 Rap1B and Rap2B translocation to the cytoskeleton by von Willebrand factor involves FcgammaII receptor-mediated protein tyrosine phosphorylation. The Journal of biological chemistry 46 10224142
2018 Rap1B promotes VEGF-induced endothelial permeability and is required for dynamic regulation of the endothelial barrier. Journal of cell science 45 29222111
2014 MicroRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B. Oncology reports 45 24626817
2010 Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. The Journal of experimental medicine 45 20733035
1991 Inhibition of ras-induced germinal vesicle breakdown in Xenopus oocytes by rap-1B. Biochemical and biophysical research communications 45 1899188
2020 Long noncoding RNA LINC00514 accelerates pancreatic cancer progression by acting as a ceRNA of miR-28-5p to upregulate Rap1b expression. Journal of experimental & clinical cancer research : CR 44 32771045
2014 miR-181 subunits enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeleton remodeling in glioblastoma cells. Medical oncology (Northwood, London, England) 43 24573637
2008 A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development. Blood 40 18319399
2004 Contribution of protease-activated receptors 1 and 4 and glycoprotein Ib-IX-V in the G(i)-independent activation of platelet Rap1B by thrombin. The Journal of biological chemistry 40 15078882
2002 High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway. The Journal of biological chemistry 40 12196513
2019 Rap1b Promotes Notch-Signal-Mediated Hematopoietic Stem Cell Development by Enhancing Integrin-Mediated Cell Adhesion. Developmental cell 39 31006651
2015 β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells. Cancer biology & therapy 39 26209110
2014 Functional analysis of miR-101-3p and Rap1b involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis. Biochemistry and cell biology = Biochimie et biologie cellulaire 36 24697700
2013 Phosphorylation of CalDAG-GEFI by protein kinase A prevents Rap1b activation. Journal of thrombosis and haemostasis : JTH 36 23611601
2016 Vasodilator-Stimulated Phosphoprotein (VASP)-dependent and -independent pathways regulate thrombin-induced activation of Rap1b in platelets. Cell communication and signaling : CCS 35 27620165
1990 Chromosome mapping of the human RAS-related RAP1A, RAP1B, and RAP2 genes to chromosomes 1p12----p13, 12q14, and 13q34, respectively. Cytogenetics and cell genetics 34 2108841
2022 SNORA70E promotes the occurrence and development of ovarian cancer through pseudouridylation modification of RAP1B and alternative splicing of PARPBP. Journal of cellular and molecular medicine 33 36056690
2018 miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b and Activating Ras-MAPK Signal. Frontiers in endocrinology 33 29599749
1992 Generation of specific antibodies against the rap1A, rap1B and rap2 small GTP-binding proteins. Analysis of rap and ras proteins in membranes from mammalian cells. European journal of biochemistry 33 1628649
2019 miR-206 inhibits thyroid cancer proliferation and invasion by targeting RAP1B. Journal of cellular biochemistry 32 31245877
2019 TRPM7 Induces Mechanistic Target of Rap1b Through the Downregulation of miR-28-5p in Glioma Proliferation and Invasion. Frontiers in oncology 32 31921670
2006 Critical role of ADP interaction with P2Y12 receptor in the maintenance of alpha(IIb)beta3 activation: association with Rap1B activation. Journal of thrombosis and haemostasis : JTH 32 16706985
1995 The association of pp125FAK, pp60Src, CDC42Hs and Rap1B with the cytoskeleton of aggregated platelets is a reversible process regulated by calcium. FEBS letters 32 7537700
2004 cAMP-dependent oncogenic action of Rap1b in the thyroid gland. The Journal of biological chemistry 31 15331589
2020 LncRNA LOXL1-AS1 promotes endometrial cancer progression by sponging miR-28-5p to upregulate RAP1B expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 32006897
2019 Function, Significance, and Regulation of Rap1b in Malignancy. Critical reviews in eukaryotic gene expression 30 31679270
2009 Phosphorylation-induced conformational changes in Rap1b: allosteric effects on switch domains and effector loop. The Journal of biological chemistry 30 19651783
2020 MicroRNA-30b-5p functions as a metastasis suppressor in colorectal cancer by targeting Rap1b. Cancer letters 29 32112903
2016 Knockdown of Rap1b Enhances Apoptosis and Autophagy in Gastric Cancer Cells via the PI3K/Akt/mTOR Pathway. Oncology research 29 27712585
2012 The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors. Journal of signal transduction 29 22745904
1992 Phosphorylation of smg p21B/rap1B p21 by cyclic GMP-dependent protein kinase. FEBS letters 29 1551424
2013 Phosphorylation of the guanine-nucleotide-exchange factor CalDAG-GEFI by protein kinase A regulates Ca(2+)-dependent activation of platelet Rap1b GTPase. The Biochemical journal 28 23600630
2011 Statins inhibit T-acute lymphoblastic leukemia cell adhesion and migration through Rap1b. Journal of leukocyte biology 28 21233409
2017 Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 27 28520221
2016 Differences in the Phosphorylation-Dependent Regulation of Prenylation of Rap1A and Rap1B. Journal of molecular biology 27 27760305
2015 Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 26269639
2009 Role of Rap1B and tumor suppressor PTEN in the negative regulation of lysophosphatidic acid--induced migration by isoproterenol in glioma cells. Molecular biology of the cell 27 19864456
2017 LncRNA AFAP1-AS Functions as a Competing Endogenous RNA to Regulate RAP1B Expression by sponging miR-181a in the HSCR. International journal of medical sciences 25 28924375
2000 The human endogenous retrovirus K Rev response element coincides with a predicted RNA folding region. RNA (New York, N.Y.) 25 11105755
2017 RAP1B, a DVL2 binding protein, activates Wnt/beta-catenin signaling in esophageal squamous cell carcinoma. Gene 24 28119087
1996 Different effects of various phospholipids on Ki-Ras-, Ha-Ras-, and Rap1B-induced B-Raf activation. The Journal of biological chemistry 22 8663012
1996 The S29 ribosomal protein increases tumor suppressor activity of K rev-1 gene on v-K ras-transformed NIH3T3 cells. Biochimica et biophysica acta 22 8781548
2008 Targeting of the small GTPase Rap2b, but not Rap1b, to lipid rafts is promoted by palmitoylation at Cys176 and Cys177 and is required for efficient protein activation in human platelets. Cellular signalling 21 18582561
1994 Correlated expression of the 97 kDa sarcoendoplasmic reticulum Ca(2+)-ATPase and Rap1B in platelets and various cell lines. The Biochemical journal 21 8297341
2018 Rap1b enhances the invasion and migration of hepatocellular carcinoma cells by up-regulating Twist 1. Experimental cell research 20 29559227
2018 Potentially critical roles of TNPO1, RAP1B, ZDHHC17, and PPM1B in the progression of coronary atherosclerosis through microarray data analysis. Journal of cellular biochemistry 20 30269354
2020 Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton's jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis. Stem cell research & therapy 18 33261656
2009 Rap1b is critical for glycoprotein VI-mediated but not ADP receptor-mediated alpha2beta1 activation. Journal of thrombosis and haemostasis : JTH 18 19192113
1992 Epinephrine suppresses rap1B.GAP-activated GTPase activity in human platelets. Proceedings of the National Academy of Sciences of the United States of America 18 1313568
2023 Lipid Deposition and Progesterone Synthesis Are Increased by miR-181b-5p through RAP1B/ERK1/2 Pathway in Chicken Granulosa Cells. Journal of agricultural and food chemistry 17 37602643
2019 miR-200b/c-RAP1B axis represses tumorigenesis and malignant progression of papillary thyroid carcinoma through inhibiting the NF-κB/Twist1 pathway. Experimental cell research 17 31877303
2018 Deletion of Rap1b, but not Rap1a or Epac1, Reduces Protein Kinase A-Mediated Thyroid Cancer. Thyroid : official journal of the American Thyroid Association 16 29882482
2013 Segmental assembly of fibronectin matrix requires rap1b and integrin α5. Developmental dynamics : an official publication of the American Association of Anatomists 16 23192979
2013 Longest neurite-specific activation of Rap1B in hippocampal neurons contributes to polarity formation through RalA and Nore1A in addition to PI3-kinase. Genes to cells : devoted to molecular & cellular mechanisms 16 24165023
1994 Analysis of the tumor suppressor activity of the K-rev-1 gene in human tumor cell lines. Cancer research 16 8275494
2022 Avian Hepatitis E Virus ORF2 Protein Interacts with Rap1b to Induce Cytoskeleton Rearrangement That Facilitates Virus Internalization. Microbiology spectrum 14 35138149
2015 The structure and conformational switching of Rap1B. Biochemical and biophysical research communications 14 25935485
2001 Identification of up-regulated Ras-like GTPase, Rap1b, by suppression subtractive hybridization. Kidney international 14 11737587
1996 Differential up-regulation of Rap1a and Rap1b proteins during smooth muscle cell cycle. European journal of cell biology 14 8832211
1995 Platelet rap1B phosphorylation is a sensitive marker for the action of cyclic AMP- and cyclic GMP-increasing platelet inhibitors and vasodilators. Journal of cardiovascular pharmacology 14 7596121
1993 Cytoskeletal interactions of Rap1b in platelets. Advances in experimental medicine and biology 14 8209787
2022 Rap1b-loss increases neutrophil lactate dehydrogenase activity to enhance neutrophil migration and acute inflammation in vivo. Frontiers in immunology 13 36505495