Affinage

RAP1B

Ras-related protein Rap-1b · UniProt P61224

Length
184 aa
Mass
20.8 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 53 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAP1B is a Ras-family small GTPase that cycles between an inactive GDP-bound and active GTP-bound state to function as a spatially regulated signaling switch controlling integrin-dependent adhesion across platelets, leukocytes, endothelium, and neurons (PMID:15696195, PMID:21940635, PMID:20733035). In platelets it is the central node for integrin αIIbβ3 inside-out and outside-in activation, secretion, and clot retraction, and its loss causes a bleeding defect with protection from arterial thrombosis (PMID:15696195, PMID:21940635). Activation is achieved by distinct guanine-nucleotide exchange factors reading different second messengers: a Gi/P2Y12-PI3K-PtdIns(3,4,5)P3 axis and Ca2+/PKC signaling through CalDAG-GEFI in platelets (PMID:11970953, PMID:11815620, PMID:12407113, PMID:16357324), cAMP through EPAC, whose mid-exchange complex with RAP1B has been resolved structurally (PMID:18660803, PMID:26269639). Once GTP-loaded, RAP1B binds the talin-F0 domain at the membrane to recruit talin and drive integrin activation, adhesion, and spreading (PMID:29170462), and engages downstream effectors including B-Raf to stimulate MEK/ERK signaling (PMID:8576107, PMID:20733035). RAP1B activity is gated negatively by GAP-stimulated hydrolysis (PMID:1313568) and by PKA/PKG phosphorylation at Ser179, which allosterically perturbs the switch I/II regions and, by reducing SmgGDS-607 binding, suppresses prenylation and membrane localization (PMID:1696481, PMID:8463283, PMID:1551424, PMID:19651783, PMID:23716716); PKA additionally inhibits RAP1B indirectly by phosphorylating CalDAG-GEFI (PMID:23611601, PMID:23600630). Inactive GDP-bound RAP1B is ubiquitinated by Smurf2 for proteasomal degradation, and this turnover, balanced by mTOR, spatially restricts RAP1B to a single neurite tip to specify axonal identity upstream of Cdc42 and the Par complex (PMID:17318188, PMID:18842593, PMID:15286792). In endothelium RAP1B specifically mediates VEGF-induced barrier dissolution and supports vascular tone via NO release and myosin phosphatase regulation (PMID:24790136, PMID:29222111). RAP1B has not been linked to a Mendelian disease within this corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1990 High

    Established that RAP1B is a direct, physiological substrate of cAMP-dependent kinase signaling, distinguishing it from Rap1A and providing the first regulatory handle on the protein.

    Evidence 32P labeling and peptide sequencing of phosphorylated protein from intact human platelets; cytoskeletal fractionation with thrombin/A23187

    PMID:1696481 PMID:2123187

    Open questions at the time
    • Functional consequence of phosphorylation not yet defined
    • Exact phosphoacceptor residue not yet mapped
  2. 1993 High

    Pinpointed Ser179 as the PKA/PKG phosphorylation site and showed RAP1B is also a CaM kinase Gr substrate, defining the precise modified residue and broadening the kinase set.

    Evidence Site-directed mutagenesis with mobility-shift, in vitro PKG kinase assay, and CaM kinase Gr substrate specificity panel

    PMID:1551424 PMID:1901412 PMID:8463283

    Open questions at the time
    • Downstream effect of Ser179 phosphorylation on GTPase activity not established
    • Physiological role of CaM kinase Gr phosphorylation in neurons unresolved
  3. 1992 Medium

    Showed that agonists tune RAP1B nucleotide state and that it physically partners with rasGAP, linking RAP1B to receptor signaling and a candidate inactivating GAP.

    Evidence GTP hydrolysis assay with α2-adrenergic pharmacology; rasGAP co-immunoprecipitation in thrombin-stimulated platelets

    PMID:1313568 PMID:1323853

    Open questions at the time
    • rasGAP Co-IP is single, without reciprocal validation
    • Functional consequence of the rasGAP/PLC-γ1 complex unresolved
  4. 1995 Medium

    Demonstrated agonist-dependent GTP loading of RAP1B in intact cells, formally establishing it as a signal-activated GTPase.

    Evidence Guanine nucleotide binding (GTP/GDP ratio) on immunoprecipitated RAP1B from cAMP-stimulated cells

    PMID:7737967

    Open questions at the time
    • GEF responsible for cAMP-driven activation not identified here
    • Downstream effectors not defined
  5. 1996 High

    Identified B-Raf as a direct RAP1B effector, connecting RAP1B to the MEK/ERK cascade in a nucleotide- and lipid-modification-dependent manner.

    Evidence Cell-free B-Raf kinase assay with GTP/GDP and lipid-modified/unmodified recombinant RAP1B, MEK phosphorylation readout

    PMID:8576107

    Open questions at the time
    • In-cell relevance of RAP1B→B-Raf not established here
    • Whether RAP1B activates or antagonizes ERK in different cell types unresolved
  6. 2002 High

    Dissected the platelet activation pathway, placing RAP1B downstream of Gi/P2Y12 and PI3K-generated PtdIns(3,4,5)P3 and showing it controls integrin αIIbβ3 affinity.

    Evidence Multiple Gα and PI3K knockout mouse platelets, receptor-selective antagonists, lipid rescue, and Rap1-GTP pull-down; megakaryocyte fibrinogen-binding with active/dominant-negative mutants and actin inhibitors

    PMID:11815620 PMID:11970953 PMID:11994301 PMID:12407113

    Open questions at the time
    • Identity of the relevant Gi-coupled GEF not established
    • How PtdIns(3,4,5)P3 connects to RAP1B exchange unresolved
  7. 2005 High

    Provided genetic proof that RAP1B is required for integrin inside-out activation and hemostasis, and identified CalDAG-GEFI as the GEF coupling Ca2+/PKC and collagen-integrin signaling to RAP1B.

    Evidence Rap1b knockout mouse with aggregation, integrin activation, and in vivo thrombosis assays; CalDAG-GEFI-deficient platelets in α2β1 outside-in signaling

    PMID:15696195 PMID:16357324

    Open questions at the time
    • Precise effector linking RAP1B to integrin affinity not yet defined here
    • Distinction between inside-out and outside-in RAP1B pools unresolved
  8. 2008 High

    Resolved the cAMP-activated EPAC2–RAP1B exchange mechanism at atomic resolution, explaining how cyclic nucleotide binding triggers nucleotide exchange.

    Evidence X-ray crystallography and single-particle EM of Epac2–cAMP–RAP1B

    PMID:18660803

    Open questions at the time
    • EPAC1 (the neuronal GEF) not structurally captured
    • In-cell kinetics of the trapped intermediate not addressed
  9. 2008 High

    Extended RAP1B function to immune cell adhesion and trafficking, defining isoform-specific roles in NK cell signalosome assembly and B/neutrophil migration.

    Evidence Rap1b knockout mouse leukocytes; LFA1 polarization, MTOC, IQGAP1/B-Raf/ERK co-IP and Western; chemotaxis, homing, and transmigration assays

    PMID:18319399 PMID:20733035 PMID:25092872

    Open questions at the time
    • Mechanism of IQGAP1 signalosome assembly not fully resolved
    • How RAP1B negatively gates PI3K/Akt via SHP-1 unconfirmed structurally
  10. 2009 High

    Defined the allosteric structural basis by which Ser179 phosphorylation perturbs the catalytic switch regions, mechanistically linking PKA/PKG to RAP1B regulation.

    Evidence Hydrogen/deuterium exchange mass spectrometry of phosphorylated RAP1B and S179D phosphomimetic

    PMID:19651783

    Open questions at the time
    • Functional consequence of switch perturbation on effector binding not directly measured
    • Reversal by phosphatase in vivo not addressed
  11. 2007 High

    Established the Smurf2/mTOR turnover axis that spatially restricts RAP1B to a single neurite tip, explaining how RAP1B specifies a single axon upstream of Cdc42/Par.

    Evidence RNAi, ubiquitination and proteasome-rescue assays, mTOR pharmacology, and spatial imaging in hippocampal neurons; EPAC1 KO and FRET activity mapping

    PMID:15286792 PMID:17318188 PMID:18842593 PMID:24165023 PMID:26269639

    Open questions at the time
    • GEF/GAP machinery localizing RAP1B activity to the tip incompletely defined
    • How EPAC1 and Smurf2 are coordinated spatially unresolved
  12. 2013 High

    Resolved a dual mechanism by which PKA inhibits RAP1B: direct Ser179 phosphorylation that suppresses prenylation via reduced SmgGDS-607 binding, and phosphorylation of the upstream GEF CalDAG-GEFI.

    Evidence A2B/βAR agonist treatment, SmgGDS co-IP, prenylation and fractionation assays; MS site-mapping and phosphomimetic mutagenesis of CalDAG-GEFI in HEK293 and platelets

    PMID:23600630 PMID:23611601 PMID:23716716 PMID:28119087

    Open questions at the time
    • Relative in vivo contributions of direct vs GEF-level inhibition unresolved
    • Note: idx 42 (DVL2) is a distinct interaction; consolidation here is editorial
  13. 2017 High

    Defined the structural basis of RAP1B-driven integrin activation by capturing the membrane-dependent talin-F0 interaction.

    Evidence X-ray crystallography of RAP1B–talin-F0, vesicle-binding assays, mutagenesis, and adhesion/spreading phenotypes

    PMID:29170462

    Open questions at the time
    • Whether other talin domains contribute to RAP1B-dependent activation not addressed
    • Cell-type generality of the talin-F0 route unresolved
  14. 2018 High

    Demonstrated isoform-specialized endothelial functions, with RAP1B mediating VEGF-induced barrier dissolution and vascular tone while RAP1A maintains basal junctions.

    Evidence Endothelial-specific Rap1A/Rap1B knockout mice, impedance sensing, VE-cadherin imaging, in vivo permeability; vascular tone, NO, and myosin phosphatase assays

    PMID:21776404 PMID:24790136 PMID:29222111

    Open questions at the time
    • Effectors mediating VEGF-specific barrier dissolution not identified
    • Mechanism distinguishing RAP1A vs RAP1B junctional pools unresolved
  15. 2018 High

    Provided in vivo genetic evidence that RAP1B is a downstream effector of PKA in tumorigenesis and a developmental regulator of skeletal and hematopoietic fate.

    Evidence Isoform-specific compound KO mice in thyroid carcinogenesis; Rap1b KO skeletal phenotyping with Axin2/BMP epistasis; zebrafish rap1b loss in HSC specification

    PMID:28520221 PMID:29882482 PMID:31006651

    Open questions at the time
    • Molecular effectors of RAP1B in chondrogenesis vs osteogenesis incompletely defined
    • How RAP1B integrates with Notch/integrin β1 in HSC niche unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct GEFs, GAPs, phosphorylation, and Smurf2-mediated degradation are spatiotemporally coordinated to generate cell-type-specific RAP1B activity pools, and which effectors dominate in each context, remains incompletely defined.
  • No unified model of context-specific effector selection
  • GAPs acting on RAP1B in non-platelet cells largely unidentified
  • Quantitative interplay of phosphorylation and ubiquitination not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0003924 GTPase activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2 GO:0005768 endosome 1
Pathway
R-HSA-109582 Hemostasis 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
BRAFCRKLDVL2IQGAP1RASA1SMGGDSTLN1

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Rap1B localizes to the tip of a single neurite in rat hippocampal neurons and is necessary and sufficient to specify axonal identity, acting upstream of Cdc42 and the Par complex (Par3/Par6/aPKC) in neuronal polarity establishment. GTPase dominant-active/dominant-negative mutants, RNA interference, live imaging of neuronal cultures Nature neuroscience High 15286792
2005 Rap1b is required downstream of GPCR-linked and GPCR-independent agonists for integrin αIIbβ3 inside-out activation and platelet aggregation; Rap1b-null mice have a bleeding defect and are protected from arterial thrombosis. Rap1b knockout mouse, platelet aggregation assays, integrin activation assays (fibrinogen binding), in vivo thrombosis model The Journal of clinical investigation High 15696195
2002 Rap1B is activated in platelets via Gαi-family members (Gαz and Gαi2) and this activation is dependent on PI3Kγ-generated phosphoinositides downstream of Gi-coupled receptors (P2Y12 for ADP, α2A-adrenergic receptor for epinephrine). Platelets from Gαz-/-, Gαi2-/-, Gαq-/-, and PI3Kγ-/- mice; Rap1-GTP pull-down; selective receptor inhibitors The Journal of biological chemistry High 11970953
2002 Constitutively active Rap1b (V12) augments agonist-induced fibrinogen binding to integrin αIIbβ3 in megakaryocytes through an effect on integrin affinity that requires intact actin polymerization; dominant-negative Rap1b (N17) and RapGAP suppress this binding. Retroviral transduction of GFP-Rap1b chimeras into murine megakaryocytes, fibrinogen binding assay, cytochalasin D/latrunculin A treatment The Journal of biological chemistry High 11994301
2008 X-ray crystal structure of Epac2 in complex with a cAMP analogue and RAP1B reveals that cAMP binding causes the cyclic nucleotide-binding domain to swing away from a position blocking the Rap binding site toward a docking site at the Ras exchange motif domain, trapping RAP1B mid-exchange reaction. X-ray crystallography, single-particle electron microscopy Nature High 18660803
2017 Talin-F0 domain binds Rap1b like canonical Rap1 effectors despite little sequence homology; this interaction becomes strong upon attachment of activated Rap1b to vesicular membranes, providing a membrane-targeting mechanism for talin to activate integrin. Disruption of the Rap1b-talin interaction strongly impairs integrin activation, cell adhesion, and cell spreading. X-ray crystallography of Rap1b–talin-F0 complex, vesicle-binding assays, mutagenesis, cell adhesion and spreading assays Nature communications High 29170462
1994 Rap1A and Rap1B proteins localize to late endocytic compartments (late endosomes/lysosomes) in fibroblasts and to phagosomes with late-endosomal features in macrophages, as shown by confocal immunofluorescence and subcellular fractionation. Confocal immunofluorescence microscopy with specific antibodies, subcellular fractionation, vaccinia T7 overexpression system Journal of cell science Medium 7962206
1996 GTP-bound, post-translationally lipid-modified Rap1B directly activates B-Raf protein kinase from bovine brain (immunoprecipitated) in a cell-free assay, stimulating MEK phosphorylation to a level comparable to Ki-Ras. Cell-free B-Raf kinase assay with recombinant Rap1B (GTP vs GDP form, lipid-modified vs unmodified), MEK phosphorylation readout The Journal of biological chemistry High 8576107
1990 Rap1B is phosphorylated by cAMP-dependent protein kinase (PKA) in intact human platelets; peptide sequencing of the purified phosphorylated protein confirms it is rap1b and not rap1a. 32P labeling of platelets, immunoprecipitation with anti-H-ras antibody (M90), proteolytic cleavage and amino acid sequencing, comparison of PKA phosphorylation kinetics of synthetic C-terminal peptides Biochemical and biophysical research communications High 1696481
1990 In resting platelets, Rap1B is membrane-associated; upon activation with thrombin or calcium ionophore A23187, Rap1B translocates quantitatively to the actin cytoskeleton fraction. Platelet fractionation (Triton X-100 lysis, differential centrifugation), Western blotting The Journal of biological chemistry High 2123187
1993 Ser179 in the C-terminal region of Rap1b is the PKA phosphorylation site; substitution with Lys (resembling Rap1a) shifts phosphorylation to Ser180. Site-directed mutagenesis, transient expression with epitope-tagged protein, cAMP stimulation and SDS-PAGE mobility shift analysis The Journal of biological chemistry High 8463283
1992 Rap1b is also phosphorylated by cGMP-dependent protein kinase (PKG) at the same Ser179 residue that is targeted by PKA. Cell-free phosphorylation assay with purified PKG and recombinant Rap1b; Km and Vmax determination FEBS letters High 1551424
1991 CaM kinase Gr (a neuron-specific Ca2+/calmodulin-dependent kinase) phosphorylates Rap1b on a serine near the C-terminus with ~1:1 stoichiometry; phosphorylation is reversed by an endogenous brain phosphatase. Other Ras-family GTPases (Rab3A, Rap2b, Ha-ras p21) are not substrates. In vitro kinase assay with purified CaM kinase Gr and Rap1b; stoichiometry determination; phosphatase reversal assay Proceedings of the National Academy of Sciences of the United States of America High 1901412
1995 cAMP-elevating agents (cholera toxin, IBMX, forskolin) activate Rap1b in intact cells, as measured by increased Rap1b-bound GTP/GDP ratio, demonstrating agonist-dependent Rap1b activation for the first time. Guanine nucleotide binding assay (GTP/GDP ratio) on immunoprecipitated Rap1b from 32P-labeled cells The Journal of biological chemistry Medium 7737967
2002 cAMP inhibition of Akt activity in thyroid cells requires both PKA-mediated activation and phosphorylation of Rap1b; dominant-negative Rap1b blocks cAMP-induced Akt inhibition. Dominant-negative Rap1b expression, cAMP stimulation, Akt kinase activity assay in PCCL3 thyroid cells The Journal of biological chemistry Medium 12089143
2002 cAMP-dependent mitogenic G1/S entry in thyroid follicular cells requires both PKA-mediated phosphorylation and activation of Rap1b; blocking either phosphorylation or GTP binding of Rap1b is sufficient to abrogate the cAMP mitogenic response. Expression of phosphorylation-deficient and activation-deficient Rap1b mutants in PCCL3 cells, DNA synthesis assay (BrdU/thymidine incorporation) Proceedings of the National Academy of Sciences of the United States of America Medium 11959997
2007 Ubiquitin E3 ligase Smurf2 ubiquitinates inactive (GDP-bound) Rap1B and targets it for proteasomal degradation. This degradation restricts Rap1B to a single neurite tip, ensuring formation of a single axon. Smurf1 regulates Rho but not Rap1B. RNAi knockdown of Smurf1/Smurf2, ubiquitination assay, proteasome inhibitor rescue, imaging of Rap1B localization in hippocampal neurons The EMBO journal High 17318188
2008 PI3K and Rheb/mTOR pathway act upstream of Rap1B to control neuronal polarity; mTOR promotes Rap1B protein levels by counteracting Smurf2-mediated degradation. Inhibiting mTOR or expressing mTOR-insensitive 4E-BP1 reduces Rap1B and blocks axon formation. RNAi of Rheb, mTOR inhibitor (rapamycin), mTOR-insensitive 4E-BP1 mutants, Rap1B protein level quantification in hippocampal neurons The Journal of biological chemistry Medium 18842593
2002 A Gi-dependent pathway (via P2Y12 receptor, not P2Y1) is necessary and sufficient to activate Rap1B in platelets; Gq-mediated Ca2+ signaling alone is insufficient for Rap1B activation through P2Y12. Rap1B-GTP pull-down assay in human platelets; selective P2Y12 and P2Y1 antagonists; ADP scavengers; epinephrine and serotonin receptor agonists The Journal of biological chemistry High 11815620
2002 Gi-dependent activation of Rap1B in platelets requires PI3K-generated PtdIns(3,4,5)P3 (but not PtdIns(3,4)P2), but is independent of adenylyl cyclase inhibition and cAMP changes. PI3Kγ is not the relevant isoform in mouse platelets. Wortmannin/LY294002 inhibition, PI3Kγ-/- mouse platelets, exogenous PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rescue, dideoxyadenosine/SQ22536 control; Rap1B-GTP pull-down The Journal of biological chemistry High 12407113
2013 Adenosine A2B receptor activation promotes PKA-mediated phosphorylation of Rap1B, which decreases its interaction with the chaperone SmgGDS-607, suppresses Rap1B prenylation, causes cytosolic/nuclear accumulation of non-prenylated Rap1B, and promotes cell scattering. A2B receptor agonist treatment, PKA inhibitors, co-immunoprecipitation of Rap1B-SmgGDS, prenylation assay, subcellular fractionation, cell scattering assay; validated in breast/lung/pancreatic cancer lines Science signaling High 23716716
2015 β-adrenergic receptor (βAR) activation via Gαs/PKA phosphorylates Rap1B, inhibits its prenylation and membrane localization, reduces cell-cell adhesion, and promotes breast cancer cell scattering; propranolol (βAR blocker) decreases cell migration. Cholera toxin and βAR agonist treatment, Western blot for Rap1B phosphorylation, prenylation assay, membrane fractionation, cell-cell adhesion and scattering assay Cancer biology & therapy Medium 26209110
1992 Epinephrine, acting through the α2-adrenergic receptor, specifically suppresses Rap1B.GAP-stimulated GTPase activity in platelet lysates (without affecting Ras.GAP or Rap2B.GAP activities), as shown by selective α2-adrenergic antagonist yohimbine blockade. [γ-32P]GTP hydrolysis assay on Rap1B immunoprecipitated from lysates of epinephrine-stimulated platelets; yohimbine antagonism; UK14304 agonist confirmation Proceedings of the National Academy of Sciences of the United States of America Medium 1313568
1992 Rap1B co-immunoprecipitates with rasGAP upon thrombin stimulation of platelets, forming a signaling complex with rasGAP and phospholipase C-γ1. Immunoprecipitation of rasGAP followed by Western blot for Rap1B; co-precipitation in resting vs thrombin-stimulated platelets Proceedings of the National Academy of Sciences of the United States of America Medium 1323853
1999 von Willebrand factor (vWF) induces translocation of Rap1B (in a later phase than Rap2B) to the platelet cytoskeleton via glycoprotein Ib and FcγRII receptor-mediated tyrosine phosphorylation; translocation is blocked by cytochalasin D, anti-FcγRII antibody, and tyrosine kinase inhibitors. Platelet fractionation, Western blotting, neutralizing antibodies against GPIb and FcγRII, cytochalasin D, tyrosine kinase inhibitor genistein The Journal of biological chemistry Medium 10224142
2011 Rap1b plays a role in both αIIbβ3 inside-out signaling/platelet secretion (granule ATP release, P-selectin expression) and αIIbβ3 outside-in signaling (platelet spreading on fibrinogen, clot retraction); outside-in Rap1b activation is Src-, PKC-, and Ca2+-dependent but independent of P2Y12 or TXA2 receptors. Rap1b-/- platelets, ATP secretion assay, P-selectin expression (FACS), spreading on fibrinogen, clot retraction, selective Src inhibitor PP2, PKC inhibitor, Ca2+ chelator, P2Y12/TXA2 KO platelets The Journal of biological chemistry High 21940635
2005 Integrin α2β1 outside-in signaling activates Rap1b via PLC-derived Ca2+ and PKC through the exchange factor CalDAG-GEFI; activated Rap1b then mediates inside-out activation of αIIbβ3 (fibrinogen binding). CalDAG-GEFI-deficient platelets fail to activate Rap1b downstream of α2β1. Platelet adhesion to α2β1 ligands, Rap1b-GTP pull-down, CalDAG-GEFI-/- mouse platelets, PLC inhibitor U73122, Ca2+ and PKC pathway dissection Blood High 16357324
2009 PKA phosphorylation at Ser179 induces allosteric conformational changes in Rap1b's switch I and switch II loops (distal from the phosphorylation site), as detected by amide hydrogen/deuterium exchange mass spectrometry; phosphomimetic S179D reproduces these changes. Hydrogen/deuterium exchange mass spectrometry (DXMS) on PKA-phosphorylated Rap1b vs S179D phosphomimetic mutant The Journal of biological chemistry High 19651783
2013 PKA phosphorylates CalDAG-GEFI at S587 (major site) and S116/117 (minor sites), and this phosphorylation abolishes CalDAG-GEFI-mediated Rap1b activation; complete abrogation of PKA-mediated Rap1b inhibition requires mutation of all three sites. Radioactive phosphate incorporation, mass spectrometry, phospho-specific antibody, phosphomimetic and alanine mutants in HEK293 and platelets, Rap1-GTP pull-down assay Journal of thrombosis and haemostasis High 23611601
2013 PKA phosphorylates CalDAG-GEFI at Ser116 and Ser586, inhibiting its ability to activate Rap1b in response to Ca2+ ionophore; phospho-mimetic S586D CalDAG-GEFI abolishes agonist-induced Rap1b activation and platelet aggregation. In vitro PKA phosphorylation of recombinant CalDAG-GEFI, alanine/aspartate mutants, Rap1b-GTP pull-down in HEK293 cells and platelets The Biochemical journal High 23600630
2016 VASP forms a complex with the adaptor Crkl via VASP's SH3-binding proline-rich region; PKA-mediated phosphorylation of VASP at Ser157 abrogates VASP-Crkl binding. VASP-null platelets show reduced agonist-induced Rap1b activation, placing the C3G/Crkl/VASP complex upstream of Rap1b. Co-immunoprecipitation, confocal microscopy of spreading platelets, GST pull-down with Crkl SH3 domains, VASP-null mouse platelets, Rap1b-GTP pull-down Cell communication and signaling Medium 27620165
2008 Rap1b is the dominant isoform in NK cells; its absence impairs LFA1 polarization, spreading, MTOC formation, and cytokine/chemokine production. Upon activation, Rap1b co-localizes with IQGAP1 and facilitates sequential phosphorylation of B-Raf, C-Raf, and ERK1/2, forming a large signalosome in the perinuclear region. Rap1a/Rap1b KO mice, LFA1 polarization assay, MTOC staining, cytokine assays, co-immunoprecipitation of Rap1b-IQGAP1, B-Raf/C-Raf/ERK phosphorylation Western blot The Journal of experimental medicine High 20733035
2008 Rap1b deficiency impairs B cell adhesion to stromal cells, reduces chemotaxis to SDF-1 and CXCL13, and decreases in vivo B cell homing to lymph nodes; Rap1b-deficient B cells show impaired SDF-1-mediated Pyk2 activation but normal ERK, p38, and Akt activation via BCR or LPS. Rap1b KO mouse, adhesion assay, chemotaxis assay, in vivo homing assay, Pyk2 phosphorylation Western blot Blood High 18319399
2014 Rap1b deficiency in neutrophils promotes transcellular (rather than paracellular) diapedesis through endothelial cells via enhanced PI3K-Akt activation and invadopodia-like protrusions; in vivo, this leads to enhanced neutrophil lung recruitment and susceptibility to endotoxin shock. The inhibitory effect of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Rap1b-/- mice, neutrophil transmigration assays, Akt inhibitor rescue in vivo, SHP-1 activity assay, invadopodia imaging The Journal of experimental medicine High 25092872
2014 Rap1b in both smooth muscle cells and endothelium is required for normal vascular tone and blood pressure; its loss leads to increased smooth muscle contractility (with increased inhibitory phosphorylation of myosin phosphatase), decreased cAMP/Epac-dependent relaxation, and reduced endothelial NO-dependent vasodilation. Rap1b-/- mice, blood pressure monitoring, aortic ring contraction/relaxation assays, myosin phosphatase phosphorylation (Western blot), nitric oxide vasodilation assay Arteriosclerosis, thrombosis, and vascular biology High 24790136
2018 Rap1b deficiency abolishes VEGF-induced endothelial barrier dissolution and AJ remodeling in vitro, while Rap1A deficiency (not Rap1b) increases basal vascular permeability; both isoforms are required for de novo AJ formation and recovery from LPS-induced barrier disruption. EC-specific Rap1A and Rap1B KO mice, electrical impedance sensing, VE-cadherin immunostaining, in vivo VEGF permeability assay, STZ-induced diabetes model Journal of cell science High 29222111
2015 EPAC (exchange protein directly activated by cAMP) activates Rap1b to specify and elongate the axon in hippocampal neurons; EPAC1 KO neurons have axon elongation and polarization defects; pharmacological EPAC activation (8-pCPT) induces supernumerary axons via Rap1b. EPAC1 KO mice neurons, shRNA knockdown, EPAC pharmacological activator (8-pCPT), axon markers (ankyrinG, synaptophysin), dominant-negative/active Rap1b The Journal of neuroscience Medium 26269639
2013 Rap1B activity is specifically elevated at the tip of the future axon (longest neurite) as shown by FRET imaging; effector mutant analysis identifies RalA and Nore1A as downstream targets of one pathway and PI3K as a target of another, both contributing to supernumerary axon formation. FRET imaging in hippocampal neurons, Rap1B effector-loop mutants (G12V/E37G and G12V/Y40C), dominant-negative RalA, Nore1A RNAi Genes to cells Medium 24165023
2002 High glucose activates and up-regulates Rap1b in renal mesangial cells via a PKC-dependent mechanism; activated Rap1b then drives fibronectin synthesis through B-Raf (not Raf-1). Rap1b dominant-negative mutants (S17N or T61R) block high-glucose-induced fibronectin synthesis. Rap1b overexpression and dominant-negative mutant transfection in mesangial cells, PKC inhibitors, B-Raf/Raf-1 Western blot, fibronectin mRNA/protein quantification The Journal of biological chemistry Medium 12196513
2008 Rap1b activates B-Raf and promotes Bcl-2 interaction (via the BH4 domain) in renal tubular cells, partially preventing high-glucose-induced mitochondrial dysfunction and apoptosis; Rap1b GTPase activity is decreased in diabetic kidneys. Rap1b overexpression in HK-2 cells, Western blot for Bcl-2/Bax, co-immunoprecipitation of Bcl-2-Rap1b, BH4 domain deletion mutant, GTPase activity assay, mitochondrial morphology (EM) Journal of the American Society of Nephrology Medium 18753253
2003 GTP-bound active Rap1B translocates to the nucleus in squamous cell carcinoma cells (not the GDP-bound form), as shown by GFP-tagged constitutively active vs inactive Rap1b mutants; nuclear translocation is also induced by growth factors. GFP-Rap1b transfection (constitutively active V12 vs dominant-negative N17), confocal microscopy, subcellular fractionation Oncogene Medium 13679863
2009 In glioma cells, the cAMP/Epac/Rap1B pathway mediates isoproterenol-induced suppression of LPA-stimulated cell migration by inhibiting Rac1; this inhibitory action requires expression of PTEN, suggesting that PTEN-mediated reduction of PI3K activity is involved in Rap1B-dependent Rac1 inhibition. siRNA knockdown of Rap1B, dominant-negative Rap1B, Epac activator, Rac1 activation assay, PTEN expression analysis, migration assay Molecular biology of the cell Medium 19864456
2017 RAP1B interacts with DVL2 (a Wnt pathway component) and activates β-catenin/TCF signaling in esophageal squamous cell carcinoma cells. Co-immunoprecipitation of RAP1B-DVL2, TCF reporter assay, gain- and loss-of-function experiments in ESCC cells Gene Medium 28119087
2017 Rap1b acts downstream of Axin2 and BMP signaling to promote chondrogenic fate while inhibiting MAPK (FGF) signaling and osteoblast differentiation; genetic deletion of Rap1b in mice causes defects in craniofacial and body skeletons due to impaired chondrocyte and enhanced osteoblast differentiation. Rap1b KO mouse, conditional Axin2 ablation, genetic epistasis analysis, MAPK signaling Western blot, chondrogenic/osteogenic differentiation assays Journal of bone and mineral research Medium 28520221
2018 Deletion of Rap1b (but not Rap1a or Epac1) in the setting of thyroid-specific Prkar1a knockout significantly decreases thyroid size and follicular cancer incidence, identifying Rap1b as the downstream effector of PKA in thyroid carcinogenesis. Tissue-specific compound KO mice (Prkar1a; Rap1a or Rap1b or Epac1 deletion), thyroid histology and tumor quantification Thyroid High 29882482
2019 In zebrafish, Rap1b stimulates integrin β1 to enhance PLPM cell adhesion to fibronectin at the somite boundary, facilitating physical contact with Notch-ligand-expressing somitic cells and thereby promoting Notch-mediated hemogenic endothelium specification and HSC development. Zebrafish rap1b knockdown/knockout, integrin β1 activation assay, cell adhesion to fibronectin, Notch reporter assay, live imaging of PLPM migration Developmental cell Medium 31006651
2016 Unlike Rap1B, phosphorylation in the polybasic region (PBR) of Rap1A does not inhibit its prenylation or binding to SmgGDS-607; GPCR-mediated suppression of Rap1A prenylation can occur independently of Rap1A phosphorylation and does not reduce Rap1A membrane localization. SmgGDS-607 binding assays with phosphorylated PBR peptides of Rap1A vs Rap1B, homology modelling, prenylation assay, membrane fractionation Journal of molecular biology Medium 27760305
2015 Crystal structures of Rap1B and mutants reveal that Rap1B crystallizes in an intermediate (not fully activated) state when bound to a non-hydrolyzable GTP analogue, and that conservative mutations distant from the nucleotide-binding site control the propensity to adopt the fully activated conformation. X-ray crystallography of Rap1B and site-directed mutants Biochemical and biophysical research communications Medium 25935485
2011 Rap1A (not Rap1B) is the predominant isoform for endothelial junction formation; Rap1A knockdown increases monolayer gaps and reduces the junctional pool of AF-6 co-immunoprecipitated, while Rap1B knockdown does not. GFP-Rap1A localizes more prominently at junctions than GFP-Rap1B. microRNA-based RNAi knockdown, electrical impedance sensing, VE-cadherin immunostaining, co-immunoprecipitation of AF-6 with GFP-Rap1A vs GFP-Rap1B, confocal microscopy Small GTPases Medium 21776404
2004 Contribution of PAR-1, PAR-4, and GPIb-IX-V to thrombin-induced Rap1B activation was established: PAR-1 and PAR-4 both signal Rap1B via ADP-dependent P2Y12 pathway; GPIb-IX-V contributes to ADP-independent Rap1B activation only when both PAR-1 and PAR-4 are co-stimulated. PAR-1/PAR-4 activating peptides, PAR desensitization, GPIb cleavage by mocarhagin, P2Y12 antagonist, P2Y12-deficient human platelets, Rap1B-GTP pull-down The Journal of biological chemistry Medium 15078882
1993 Phosphorylation of Rap1B by cAMP-dependent PKA does not inhibit its association with the cytoskeleton in thrombin-activated platelets. Platelet fractionation, Western blot, cAMP-induced phosphorylation of Rap1b prior to thrombin activation Advances in experimental medicine and biology Low 8209787
1993 Pre-phosphorylation of Rap1B by cAMP/iloprost does not inhibit platelet aggregation, ATP secretion, or responses to multiple agonists (collagen, phorbol ester, vasopressin, ADP, epinephrine), indicating that PKA-mediated Rap1B phosphorylation alone is not responsible for platelet inhibition by cyclic AMP. Iloprost pre-treatment, Western blot verification of Rap1B phosphorylation, platelet aggregation and ATP secretion with multiple agonists Cellular signalling Medium 7684600
2008 Rap1a siRNA knockdown in human microvascular endothelial cells reduces ERK, p38, and Rac activation in response to FGF2, and impairs cell adhesion, migration, and tubular structure formation; rap1b siRNA produces similar but not identical defects in adhesion and migration. siRNA knockdown of rap1a and rap1b in HMVECs, ERK/p38/Rac activation assays, adhesion/migration assays, Matrigel tube formation Molecular and cellular biology Medium 18625726

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 317 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 106 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
2017 Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nature communications 83 29170462
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
2013 An adenosine-mediated signaling pathway suppresses prenylation of the GTPase Rap1B and promotes cell scattering. Science signaling 81 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 68 13679863
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 66 36029734
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 65 28551849
2011 Isoform-specific differences between Rap1A and Rap1B GTPases in the formation of endothelial cell junctions. Small GTPases 64 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 55 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
2010 Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. The Journal of experimental medicine 46 20733035
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
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) 44 24573637
2019 Rap1b Promotes Notch-Signal-Mediated Hematopoietic Stem Cell Development by Enhancing Integrin-Mediated Cell Adhesion. Developmental cell 40 31006651
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
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
2019 TRPM7 Induces Mechanistic Target of Rap1b Through the Downregulation of miR-28-5p in Glioma Proliferation and Invasion. Frontiers in oncology 33 31921670
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 Function, Significance, and Regulation of Rap1b in Malignancy. Critical reviews in eukaryotic gene expression 32 31679270
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
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
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 29 23600630
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
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 28 28520221
2011 Statins inhibit T-acute lymphoblastic leukemia cell adhesion and migration through Rap1b. Journal of leukocyte biology 28 21233409
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 28 19864456
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
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
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
2018 Rap1b enhances the invasion and migration of hepatocellular carcinoma cells by up-regulating Twist 1. Experimental cell research 21 29559227
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 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
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 18 31877303
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
2013 Segmental assembly of fibronectin matrix requires rap1b and integrin α5. Developmental dynamics : an official publication of the American Association of Anatomists 17 23192979
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 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
2015 The structure and conformational switching of Rap1B. Biochemical and biophysical research communications 15 25935485
2022 Avian Hepatitis E Virus ORF2 Protein Interacts with Rap1b to Induce Cytoskeleton Rearrangement That Facilitates Virus Internalization. Microbiology spectrum 14 35138149
2022 Rap1b-loss increases neutrophil lactate dehydrogenase activity to enhance neutrophil migration and acute inflammation in vivo. Frontiers in immunology 14 36505495
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
2025 Dapagliflozin activates the RAP1B/NRF2/GPX4 signaling and promotes mitochondrial biogenesis to alleviate vascular endothelial ferroptosis. Cellular signalling 13 40280228
2020 Long Noncoding RNA LUADT1 Is Upregulated in Melanoma and May Sponge miR-28-5p to Upregulate RAP1B. Cancer biotherapy & radiopharmaceuticals 13 32191497
1993 Phosphorylation of rap1B by protein kinase A is not involved in platelet inhibition by cyclic AMP. Cellular signalling 13 7684600

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