Affinage

RALB

Ras-related protein Ral-B · UniProt P11234

Length
206 aa
Mass
23.4 kDa
Annotated
2026-06-10
61 papers in source corpus 27 papers cited in narrative 28 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

RALB is a RAS-superfamily small GTPase that operates as a nucleotide-dependent molecular switch downstream of RAS, coordinating membrane trafficking, innate immune/anti-apoptotic signaling, autophagy, and tumor cell motility through the exocyst complex (PMID:17018283, PMID:21241894, PMID:17174914). In its active state RALB engages two mutually exclusive exocyst-associated effectors: binding the exocyst subunit Sec5 recruits and activates the kinase TBK1 to suppress apoptosis and mediate innate immune signaling (PMID:17018283), while binding Exo84 nucleates catalytically active ULK1 and Beclin1-VPS34 complexes on the exocyst to drive autophagosome formation upon nutrient deprivation (PMID:21241894). The choice between these effector outputs is set by ubiquitylation at Lys47, which sterically blocks Exo84 while favoring Sec5; the deubiquitylase USP33 removes this mark during starvation to permit RALB-Exo84-Beclin1 assembly and autophagy (PMID:24056301). RALB membrane targeting and effector engagement are further tuned by post-translational modification of its C-terminal hypervariable region: PKCα phosphorylation at Ser198 shifts RALB from the plasma membrane to endomembranes, decreasing Sec5 association and controlling SNARE interactions, integrin trafficking, and adhesion (PMID:20940393, PMID:22393054), and lysine fatty acylation at Lys200 (reversed by SIRT2) enhances plasma-membrane localization and Sec5/Exo84 recruitment (PMID:31433161). Distinct from RALA, RALB drives vectorial cell migration via leading-edge exocyst targeting (PMID:16382162), cytokinetic abscission at the midbody (PMID:18756269), and invasion/metastasis through both the RalBP1/RLIP76 ATPase-dependent invadopodium pathway (PMID:22331470) and exocyst-mediated recruitment of the WAVE Regulatory Complex (PMID:30320548). In RAS-mutant cancers, an integrin αvβ3-KRAS-RALB axis activates TBK1 and NF-κB to support tumor initiation and drug resistance (PMID:24747441), and RALB-TBK1-BCL2 signaling sustains AML survival, including a RAS-independent CDK5-driven mode at relapse (PMID:27556501, PMID:27991934). Structural and thermodynamic analyses establish that RALB switch regions sample distinct conformational states and that Sec5, Exo84, and RLIP76 bind competitively through structurally distinct interfaces (PMID:19166349, PMID:20696399, PMID:25621740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2006 High

    Established that RALB acts through the exocyst subunit Sec5 to activate TBK1, defining a direct effector route by which RALB suppresses apoptosis and mediates innate immunity, and separately that RALB uniquely supports directed cell migration via exocyst targeting to the leading edge.

    Evidence Reciprocal Co-IP, TBK1 kinase assays, and isoform-specific siRNA with migration/exocyst-assembly readouts in cancer and migrating cells

    PMID:16382162 PMID:17018283

    Open questions at the time
    • Did not define how RALB-Sec5 relieves TBK1 autoinhibition
    • Upstream activator selecting the Sec5 versus Exo84 output not identified
  2. 2006 High

    Resolved a division of labor between Ral isoforms in pancreatic cancer, showing RALB is required for invasion and metastasis whereas RALA drives anchorage-independent growth and tumor initiation, linking RALB specifically to the invasive program downstream of RAS.

    Evidence Isoform-specific siRNA across a 10-cell-line panel, in vitro invasion assays, and tail-vein metastasis assays in mice

    PMID:17174914

    Open questions at the time
    • Effector mediating the invasion phenotype not pinpointed in this study
    • Mechanism of isoform-selective function unexplained
  3. 2007 Medium

    Showed RALB is geranylgeranylated and that this prenylation underlies its proapoptotic and growth-suppressive responses to GGTIs, and identified dense-core vesicles as a site where RALB acts as a GTP sensor for regulated exocytosis.

    Evidence GGTI-resistant prenylation-mutant rescue with survivin/p27 readouts; shRNA knockdown with GTP- versus Ca2+-dependent exocytosis assays and EM in PC12 cells

    PMID:17202486 PMID:17875936 PMID:8972729

    Open questions at the time
    • Direct membrane-anchoring contribution of geranylgeranylation versus HVR modifications not deconvolved
    • Effectors at dense-core vesicles not identified
  4. 2008 High

    Defined a RALB-specific role in the final step of cytokinesis, recruiting the exocyst to the midbody for abscission while RALA acts earlier at the furrow, with distinct RalGEFs providing the temporal input.

    Evidence Isoform-specific siRNA, live-cell imaging, midbody localization, and epistasis with RalGEF mutants

    PMID:18756269

    Open questions at the time
    • Identity of the RalGEF acting at the midbody not fully resolved
    • Membrane cargo delivered for abscission not defined
  5. 2009 High

    Provided the structural and dynamic basis of RALB effector binding, revealing that even GTP-loaded RALB samples a non-effector-competent state-1 conformation, so effector engagement is conformationally gated rather than a simple GTP-on switch.

    Evidence NMR solution structure, 31P NMR conformational analysis, and backbone dynamics of RALB-GMPPNP with effector titration

    PMID:19166349

    Open questions at the time
    • How cellular modifications bias the state-1/state-2 equilibrium unknown
    • Conformational selection by individual effectors not quantified in cells
  6. 2010 High

    Mapped the competitive architecture of RALB effector interfaces, showing RLIP76 binds the switch regions via a coiled-coil mode distinct from Sec5/Exo84 and that the three effectors compete for the active GTPase with similar affinities.

    Evidence X-ray crystallography of the RalB-RLIP76 complex, interface mutagenesis, and competitive binding assays

    PMID:20696399

    Open questions at the time
    • How effector choice is biased in vivo beyond affinity competition not addressed
    • Did not resolve regulatory inputs that partition effectors spatially
  7. 2010 High

    Identified PKC phosphorylation of RALB Ser198 in the membrane-targeting HVR as a switch that drives plasma-membrane-to-perinuclear relocalization and is required for actin organization, anchorage-independent growth, migration, and lung metastasis.

    Evidence In vitro kinase assay, MS phospho-site mapping, phosphosite mutagenesis with siRNA rescue, and in vivo metastasis assay

    PMID:20940393

    Open questions at the time
    • Counteracting phosphatase not identified here
    • Link between relocalization and metastatic output mechanistically incomplete
  8. 2012 High

    Resolved the downstream consequences of Ser198 phosphorylation and a RLIP76-dependent invasion route, showing PKCα phosphorylation reduces Sec5 binding and reroutes integrin trafficking, while invadopodium formation requires RLIP76 ATPase activity rather than its RhoGAP function.

    Evidence Phospho-site mutagenesis, Co-IP, vesicle trafficking and adhesion assays; effector-selective and ATPase-deficient RLIP76 mutants in invadopodium assays

    PMID:22331470 PMID:22393054

    Open questions at the time
    • Substrate of RLIP76 ATPase activity in invadopodia unknown
    • How phosphorylation-driven trafficking integrates with effector competition unclear
  9. 2013 High

    Established ubiquitylation at Lys47 as the molecular switch governing effector choice, sterically blocking Exo84 (autophagy) while favoring Sec5 (immunity), with USP33 acting as the starvation-induced eraser that licenses autophagy.

    Evidence Ubiquitylation site mapping, Lys47 mutagenesis, reciprocal Co-IP, and USP33 perturbation with localization studies

    PMID:24056301

    Open questions at the time
    • E3 ligase that writes the Lys47 ubiquitin mark not identified
    • Signals controlling USP33 relocalization to RalB vesicles incomplete
  10. 2014 High

    Placed RALB within an integrin αvβ3-KRAS module at the membrane that activates TBK1-NF-κB to confer tumor initiation, self-renewal, and erlotinib resistance, linking RALB effector signaling to drug-tolerant cancer states.

    Evidence Reciprocal Co-IP, plasma-membrane fractionation, gain/loss-of-function, and patient-derived xenografts with pharmacologic inhibition

    PMID:24747441

    Open questions at the time
    • How unliganded integrin recruits the KRAS-RALB complex structurally unresolved
    • Relative contribution of Sec5 versus other effectors not dissected
  11. 2015 Medium

    Extended the invasion and effector-interface picture, showing RALB drives TGFβ-induced EMT dissemination via a GEF-H1-exocyst-RhoA traction axis, and that RALB-RLIP76 versus RALB-Sec5 interfaces have distinct energetic landscapes enabling effector-selective mutations.

    Evidence siRNA with traction-force microscopy and 3D invasion assays plus Sec5-GEF-H1 Co-IP; ITC/SPR thermodynamic mutagenesis panels

    PMID:25621740 PMID:26152517

    Open questions at the time
    • GEF-H1-exocyst pathway tested in a single lab
    • Thermodynamic mapping lacked cellular functional validation
  12. 2016 Medium

    Demonstrated that RALB-TBK1-BCL2 signaling is a survival dependency in AML downstream of RAS, and that RAS-independent CDK5-mediated RALB activation drives relapse, nominating the CDK5-RALB axis as a therapeutic target.

    Evidence shRNA knockdown with phospho-TBK1/BCL2 and apoptosis readouts in NRAS-inducible AML and PDX models; CDK5 inhibition with dinaciclib

    PMID:27556501 PMID:27991934

    Open questions at the time
    • Mechanism by which CDK5 activates RALB not biochemically defined
    • Single-lab in vivo models
  13. 2018 High

    Directly linked plasma-membrane RALB activity to the actin nucleation machinery, showing optogenetically activated RALB recruits the WAVE Regulatory Complex via the exocyst to induce protrusions and invasion, with RGL1/RGL2 relaying RAS input.

    Evidence Optogenetic RalB activation, Co-IP, siRNA knockdown, and invasion assays

    PMID:30320548

    Open questions at the time
    • Direct WRC-exocyst contact interface not mapped
    • How WRC recruitment is coordinated with other effector outputs unclear
  14. 2019 Medium

    Refined the localization and modification logic of RALB, mapping active RALB and RGL2 to early/recycling endosomes and autophagosomes, identifying SIRT2-reversible Lys200 fatty acylation as a plasma-membrane targeting determinant, and implicating Ral proteins in TBK1 control at depolarized mitochondria.

    Evidence FRET biosensor and quantitative imaging with RGL2 knockdown; biochemical acylation assays and Lys200 mutagenesis with SIRT2 knockdown; live-cell relocalization and TBK1 activity assays under mitochondrial depolarization

    PMID:30995277 PMID:31222145 PMID:31433161

    Open questions at the time
    • Acyltransferase adding the Lys200 modification not identified
    • Mitochondrial TBK1 model rests on single-lab localization/activity correlation
  15. 2020 Medium

    Uncovered a pro-survival function in which RALB restrains apoptosis by preventing lysosomal degradation of the death receptor DR5, so RALB loss triggers Caspase-8-dependent death and RALB associates with the TRAIL DISC.

    Evidence siRNA/shRNA knockdown, proteomics, DR5 KO epistasis, lysosomal degradation assays, and RALB-DISC Co-IP in KRAS-mutant colorectal cells

    PMID:33122623

    Open questions at the time
    • Mechanism by which RALB routes DR5 to lysosomes undefined
    • Effector mediating DR5 trafficking not identified
  16. 2025 High

    Revealed a non-canonical exocyst engagement in endothelial Weibel-Palade body exocytosis, where RALB binds exocyst in the GDP state at rest and uncouples upon activation, with PKC phosphorylation of the HVR promoting exocyst binding and dephosphorylation augmenting exocytosis.

    Evidence siRNA knockdown, nucleotide-state and phospho-site mutants, GDP/GTP-state exocyst binding assays, PKC inhibition, and live-cell WPB exocytosis assays

    PMID:40172988

    Open questions at the time
    • Reconciliation with canonical GTP-dependent effector engagement incomplete
    • Phosphatase reversing HVR phosphorylation not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full regulatory circuit that integrates ubiquitylation, phosphorylation, and acylation of the RALB HVR with conformational state-switching to select among competing exocyst effectors in a given compartment remains to be unified, and the writer enzymes (Lys47 E3 ligase, Lys200 acyltransferase) and HVR phosphatase are unidentified.
  • No E3 ligase identified for Lys47 ubiquitylation
  • Acyltransferase for Lys200 acylation unknown
  • Quantitative model coupling PTMs to conformational state and effector partitioning absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 1 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 3 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 3 R-HSA-1640170 Cell Cycle 1
Partners
ARHGEF2/GEF-H1EXOC2/SEC5EXOC8/EXO84NF2/MERLINRALBP1/RLIP76SIRT2TBK1USP33
Complex memberships
exocyst

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 RalB directly binds its effector Sec5 (a component of the exocyst complex), and the RalB/Sec5 complex recruits and activates the atypical IκB kinase TBK1, suppressing apoptosis in cancer cells and mediating innate immune signaling upon viral infection. Co-immunoprecipitation, protein complex analysis, kinase assays, loss-of-function (siRNA), cell transformation assays Cell High 17018283
2011 RalB localizes to nascent autophagosomes and is activated upon nutrient deprivation. Through direct binding to its effector Exo84, RalB induces assembly of catalytically active ULK1 and Beclin1-VPS34 complexes on the exocyst, driving autophagosome formation and isolation membrane maturation. Subcellular fractionation/live imaging, co-immunoprecipitation, loss-of-function (siRNA/shRNA), epistasis (constitutively active RalB rescue), in vitro complex reconstitution Cell High 21241894
2006 RalB (but not RalA) is required for cell migration; RalB promotes exocyst (Sec6/8 complex) assembly and its localization to the leading edge of migrating cells, with loss of RalB impairing vectorial cell motility. siRNA loss-of-function, immunofluorescence localization, exocyst assembly assays Molecular and cellular biology High 16382162
2013 Ubiquitylation of RalB at Lys47 switches its effector preference: ubiquitylation sterically inhibits RalB binding to Exo84 (blocking autophagy) while facilitating its interaction with Sec5 (promoting TBK1-innate immunity signaling). The deubiquitylase USP33 removes this ubiquitin mark upon nutrient starvation, relocalizing to RalB-positive vesicles and enabling RalB-Exo84-Beclin1 complex formation for autophagy. Ubiquitylation mapping, mutagenesis (Lys47 mutants), co-immunoprecipitation, USP33 knockdown/overexpression, localization studies Nature cell biology High 24056301
2008 RalB (but not RalA) is required for abscission and completion of cytokinesis through recruitment of the exocyst to the midbody; distinct RalGEF proteins provide upstream input to RalB specifically at this step, whereas RalA acts earlier at the cytokinetic furrow. siRNA knockdown, live-cell imaging, subcellular localization, epistasis with RalGEF mutants The EMBO journal High 18756269
2006 RalB is required for invasion and metastasis of pancreatic cancer cells, while RalA (but not RalB) is required for anchorage-independent growth and tumor initiation; both are more commonly activated in pancreatic tumors than other Ras effector pathways. siRNA knockdown, in vitro invasion assays, tail-vein metastasis assays in mice, panel of 10 cell lines Current biology : CB High 17174914
2014 In the unliganded state, integrin αvβ3 recruits both KRAS and RalB to the tumor cell plasma membrane, leading to activation of TBK1 and NF-κB; this αvβ3-KRAS-RalB-NF-κB pathway is necessary and sufficient for tumor initiation, anchorage independence, self-renewal, and erlotinib resistance. Co-immunoprecipitation, plasma membrane fractionation, loss-of-function (siRNA/shRNA), gain-of-function, patient-derived xenografts, pharmacological inhibition Nature cell biology High 24747441
2010 Protein kinase C (PKC) phosphorylates RalB at Ser198 in its C-terminal membrane-targeting sequence, causing RalB translocation from plasma membrane to perinuclear regions; this phosphorylation is necessary for actin cytoskeletal organization, anchorage-independent growth, cell migration, and experimental lung metastasis. In vitro kinase assay, mass spectrometry phospho-site mapping, site-directed mutagenesis, phosphosite-specific antibodies, phorbol ester stimulation, siRNA rescue experiments, subcellular fractionation Cancer research High 20940393
2012 PKCα phosphorylation of RalB at Ser198 results in enhanced RalB endomembrane accumulation, decreased association with exocyst component Sec5, regulation of v- and t-SNARE interactions, control of vesicular trafficking of α5-integrin to the cell surface, and modulation of cell attachment to fibronectin. Mutagenesis, co-immunoprecipitation, subcellular fractionation, vesicle trafficking assays, cell adhesion assays The Journal of biological chemistry High 22393054
2012 RalB mediates invadopodium formation in KRAS mutant pancreatic cancer cells through RalBP1/RLIP76 (but not Sec5 or Exo84), and this function requires the ATPase activity of RalBP1 rather than its canonical GAP activity toward Rho GTPases. siRNA knockdown, dominant-negative/constitutively active mutants, ATPase-deficient RLIP76 mutants, invadopodium formation assays Molecular and cellular biology High 22331470
2015 RalB (but not RalA) is required for TGFβ-induced EMT-driven cell dissemination by acting via the RhoGEF GEF-H1, which associates with the exocyst complex. Uncoupling of exocyst subunit Sec5 from GEF-H1 impairs RhoA activation and traction force generation. siRNA knockdown, co-immunoprecipitation (Sec5-GEF-H1 interaction), traction force microscopy, 3D invasion assays Scientific reports Medium 26152517
2018 Active RalB at the plasma membrane promotes recruitment of the Wave Regulatory Complex (WRC) via the exocyst, inducing membrane protrusions and invasion; Ras signals to RalB through RalGEFs RGL1 and RGL2 to drive invasiveness. Optogenetic light-controlled RalB activation, co-immunoprecipitation, siRNA knockdown, invasion assays eLife High 30320548
2019 SIRT2 acts as a deacylase for RalB: RalB undergoes lysine fatty acylation predominantly at Lys200, which enhances plasma membrane localization and recruitment of its effectors Sec5 and Exo84 to the plasma membrane; SIRT2 removes this acylation and affects cell migration. Biochemical acylation assays, mutagenesis (Lys200), co-immunoprecipitation, subcellular fractionation, trans-well migration assays, SIRT2 knockdown ACS chemical biology Medium 31433161
2009 NMR solution structure of RalB bound to GTP analogue GMPPNP revealed that the switch regions predominantly adopt state 1 (non-effector-binding competent) in the unbound form; 31P NMR of RalB.GTP shows both states 1 and 2 are sampled, and addition of an effector only partially stabilizes state 2, revealing dynamic properties of the effector-binding switches. NMR spectroscopy (solution structure determination), 31P NMR, backbone dynamics measurements Biochemistry High 19166349
2010 The crystal structure of RalB in complex with the Ral-binding domain of RLIP76 reveals a coiled-coil binding motif that contacts both nucleotide-sensitive switch regions of RalB; this mode of binding is distinct from the Sec5 and Exo84 exocyst interactions, and Sec5, Exo84, and RLIP76 bind Ral proteins competitively with similar affinities in vitro. X-ray crystallography (structure of RalB-RLIP76 complex), affinity measurements with RalB mutants, competitive binding assays Structure High 20696399
2007 RalB (and RalA) are exclusively geranylgeranylated; inhibition of geranylgeranylation by GGTIs mediates the proapoptotic and anti-anchorage-dependent growth effects specifically through RalB (whereas inhibition of anchorage-independent growth goes through RalA). GGTI treatment of RalB suppresses survivin and induces p27Kip1. Farnesylated GGTI-resistant RalB mutants, radiolabeled prenylation assays, colony formation assays, Western blot for survivin and p27 Molecular and cellular biology Medium 17875936
2007 RalB (and RalA) localize to dense core vesicles in neuroendocrine PC12 cells and function specifically as GTP sensors required for GTP-dependent exocytosis of dense core vesicles, but are dispensable for Ca2+-dependent exocytosis or vesicle docking. Stable shRNA knockdown of RalA and RalB, GTP-dependent exocytosis assays, Ca2+-dependent exocytosis assays, electron microscopy (docking), immunolocalization on vesicles, rescue transfection The Journal of neuroscience High 17202486
2011 RalA and RalB have opposing roles in tight junction development: RalA knockdown increases paracellular permeability and reduces TJ component incorporation, while RalB knockdown decreases paracellular permeability and increases TJ component incorporation; both activities are mediated through the exocyst complex. siRNA knockdown, paracellular permeability assays, immunofluorescence of TJ components, exocyst loss-of-function epistasis Molecular biology of the cell Medium 22013078
2019 RalB and its activator RGL2 co-localize at early and recycling endosomes (and to lesser extent at autophagosomes); RalB signaling is active at these endomembrane compartments basally, and RalB activity increases at autophagosomes upon nutrient starvation. RGL2 is required for both invasion and autophagy. Quantitative automated image analysis (Endomapper), FRET-based RalB biosensor, siRNA knockdown, subcellular fractionation Scientific reports Medium 31222145
2019 RalA and RalB both relocalize to depolarized mitochondria in a clathrin-mediated endocytosis-dependent manner; genetic and pharmacologic inhibition of RalA and RalB increases TBK1 activity basally and in response to mitochondrial depolarization, suggesting a model where Ral proteins at depolarized mitochondria facilitate TBK1 activation by releasing inhibition. Live-cell imaging (relocalization upon depolarization), clathrin inhibition, siRNA/genetic knockdown, TBK1 kinase activity assays PloS one Medium 30995277
2016 RALB signaling is required for AML cell survival downstream of RAS; knockdown of RALB leads to decreased phosphorylation of TBK1 and reduced BCL2 expression, inducing apoptosis and phenocopying suppression of oncogenic RAS. Genetic knockdown (shRNA), NRAS-inducible mouse AML model, phospho-TBK1 Western blot, BCL2 Western blot, apoptosis assays, patient-derived AML samples Oncotarget Medium 27556501
2016 Ras-oncogene-independent activation of RALB (via CDK5-mediated activation) drives AML relapse; pharmacological inhibition of CDK5 with dinaciclib suppresses RALB activity and RALB-dependent TBK1 phosphorylation, inducing anti-leukemic effects. Mouse NRAS(V12)-inducible AML relapse model, RALB expression/activity assays, CDK5 inhibitor (dinaciclib) treatment, patient-derived xenografts, TBK1 phosphorylation assays Oncogene Medium 27991934
2025 RalB (but not RalA) is required for regulated exocytosis of Weibel-Palade bodies (WPBs) in endothelial cells; unlike typical GTPase-effector interactions, RalB binds exocyst in its GDP-bound state in resting cells. Upon stimulation, exocyst is uncoupled from RalB-GTP, enabling WPB tethering and exocytosis. PKC-dependent phosphorylation of RalB C-terminal HVR promotes exocyst binding, and dephosphorylation (or nonphosphorylatable mutant expression) disengages exocyst and augments WPB exocytosis. siRNA knockdown, constitutively active/dominant-negative RalB mutants, phosphorylation-site mutagenesis (nonphosphorylatable mutant), exocyst binding assays in GDP vs GTP states, PKC inhibition, live-cell exocytosis assays Molecular biology of the cell High 40172988
2004 In Xenopus early development, RalB signals to the actin cytoskeleton via RLIP (RalBP1); membrane targeting of RLIP recapitulates activated RalB phenotype (cortical actin disruption), and overexpression of the RLIP Ral-binding domain competitively blocks RalB-induced actin effects. Xenopus microinjection, dominant-negative competition (RalBD overexpression), constitutively active RalB (G23V), cortical actin/phenotype analysis Mechanisms of development Medium 15511640
2020 RALB depletion in KRAS mutant colorectal cancer cells induces Caspase-8-dependent cell death through upregulation of the death receptor DR5 (TRAIL-R2) by preventing its lysosomal degradation; TRAIL treatment causes association of RALB with the death-inducing signaling complex (DISC). siRNA/shRNA knockdown, proteomic analysis, DR5 knockout/knockdown epistasis, lysosomal degradation assays, Co-IP (RALB-DISC interaction), apoptosis assays Cell death & disease Medium 33122623
2015 Thermodynamic mapping of RalB-effector interfaces using panels of RalB and RLIP76 mutants revealed distinct energetic landscapes for RalB-RLIP76 versus RalB-Sec5 complexes, providing a physical basis for effector-selective mutations; despite identical contact residues, RalA and RalB show different energetic profiles in RLIP76 binding. Affinity measurements (ITC/SPR), site-directed mutagenesis panels of RalB and RLIP76, structure-guided interface analysis Biochemistry Medium 25621740
1996 RalA and RalB are geranylgeranylated (not farnesylated) in vitro, and both proteins distribute to the particulate fraction of human platelets, with RalB also detectable in the platelet cytosol, indicating differential subcellular distribution between the isoforms. [3H]-mevalonolactone prenylation assay with geranylgeranyl pyrophosphate inhibition, subcellular fractionation, Western blot with isoform-specific antibodies Biochimica et biophysica acta Medium 8972729
2025 Active Merlin (NF2 tumor suppressor isoforms 1 and 2) directly binds RalA and RalB in a PIP2-dependent manner at the plasma membrane, co-localizing with RalA/B. Merlin loss results in aberrant activation of RalA and RalB. Merlin competitively inhibits RalB binding to its exocyst effectors Sec5 and Exo84, and regulates the kinetics of exocytosis in a RalB-dependent manner. Proximity biotinylation, direct binding assays, co-localization, competitive binding assays (Merlin vs Sec5/Exo84 for RalB), exocytosis kinetics assays, loss-of-function (Merlin KO) bioRxivpreprint Medium

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 An integrin β₃-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition. Nature cell biology 328 24747441
2006 RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell 306 17018283
2011 RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell 257 21241894
2006 Divergent roles for RalA and RalB in malignant growth of human pancreatic carcinoma cells. Current biology : CB 192 17174914
2006 RalB mobilizes the exocyst to drive cell migration. Molecular and cellular biology 112 16382162
2005 RalA and RalB: antagonistic relatives in cancer cell migration. Cancer research 109 16103060
2008 Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs. The EMBO journal 96 18756269
2013 The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response. Nature cell biology 79 24056301
2007 Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependent growth and induce apoptosis and RalA to inhibit anchorage-independent growth. Molecular and cellular biology 68 17875936
2012 Genetic deletion of RALA and RALB small GTPases reveals redundant functions in development and tumorigenesis. Current biology : CB 65 23063435
2012 The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effector. Molecular and cellular biology 56 22331470
2010 Phosphorylation of RalB is important for bladder cancer cell growth and metastasis. Cancer research 45 20940393
2009 Solution structure and dynamics of the small GTPase RalB in its active conformation: significance for effector protein binding. Biochemistry 40 19166349
2018 RalB directly triggers invasion downstream Ras by mobilizing the Wave complex. eLife 36 30320548
2010 The RalB-RLIP76 complex reveals a novel mode of ral-effector interaction. Structure (London, England : 1993) 36 20696399
2019 SIRT2 and Lysine Fatty Acylation Regulate the Activity of RalB and Cell Migration. ACS chemical biology 31 31433161
2015 RalB regulates contractility-driven cancer dissemination upon TGFβ stimulation via the RhoGEF GEF-H1. Scientific reports 31 26152517
2015 The mucin MUC4 is a transcriptional and post-transcriptional target of K-ras oncogene in pancreatic cancer. Implication of MAPK/AP-1, NF-κB and RalB signaling pathways. Biochimica et biophysica acta 30 26477488
2024 Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis. Cell reports 29 38412097
2012 Differential involvement of RalA and RalB in colorectal cancer. Small GTPases 28 22790202
2012 Phosphorylation by protein kinase Cα regulates RalB small GTPase protein activation, subcellular localization, and effector utilization. The Journal of biological chemistry 26 22393054
2011 RalA and RalB differentially regulate development of epithelial tight junctions. Molecular biology of the cell 26 22013078
2022 The RAL Enigma: Distinct Roles of RALA and RALB in Cancer. Cells 24 35626682
2007 RalA and RalB function as the critical GTP sensors for GTP-dependent exocytosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 17202486
2008 Characterization of RalB-Sec5-TBK1 function in human oncogenesis. Methods in enzymology 22 18413258
2020 RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma. Chinese medicine 21 32577124
2010 Ras-related small GTPases RalA and RalB regulate cellular survival after ionizing radiation. International journal of radiation oncology, biology, physics 19 20619549
2012 RalA and RalB proteins are ubiquitinated GTPases, and ubiquitinated RalA increases lipid raft exposure at the plasma membrane. The Journal of biological chemistry 17 22700969
2006 RalB signaling: a bridge between inflammation and cancer. Cell 17 17018274
2004 RLIP mediates downstream signalling from RalB to the actin cytoskeleton during Xenopus early development. Mechanisms of development 17 15511640
1996 Generation of antibodies specific for the RalA and RalB GTP-binding proteins and determination of their concentration and distribution in human platelets. Biochimica et biophysica acta 17 8972729
2024 A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility. Nature communications 15 38519457
2020 MicroRNA-139 inhibits pancreatic-cancer carcinogenesis by suppressing RalB via the Ral/RAC/PI3K pathway. Archives of biochemistry and biophysics 15 33290747
2011 Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model. Cancer cell international 15 21714887
2010 Involvement of RhoA and RalB in geranylgeranyltransferase I inhibitor-mediated inhibition of proliferation and migration of human oral squamous cell carcinoma cells. Cancer chemotherapy and pharmacology 14 21107573
1999 Characterization of Xenopus RalB and its involvement in F-actin control during early development. Developmental biology 14 10328920
2017 Targeting Ras signaling in AML: RALB is a small GTPase with big potential. Small GTPases 13 28682649
2020 RALB GTPase: a critical regulator of DR5 expression and TRAIL sensitivity in KRAS mutant colorectal cancer. Cell death & disease 12 33122623
2000 Tissue-specific expression of GTPas RalA and RalB during embryogenesis and regulation by epithelial-mesenchymal interaction. Mechanisms of development 12 11025226
2017 A fully automated procedure for the parallel, multidimensional purification and nucleotide loading of the human GTPases KRas, Rac1 and RalB. Protein expression and purification 10 28137655
1998 Identification and characterization in Xenopus of XsmgGDS, a RalB binding protein. Biochemical and biophysical research communications 9 9753634
2016 Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia. Oncogene 8 27991934
2019 RalA and RalB relocalization to depolarized mitochondria depends on clathrin-mediated endocytosis and facilitates TBK1 activation. PloS one 7 30995277
2019 Localization of RalB signaling at endomembrane compartments and its modulation by autophagy. Scientific reports 7 31222145
2016 RALB provides critical survival signals downstream of Ras in acute myeloid leukemia. Oncotarget 6 27556501
2015 Involvement of RalB in the effect of geranylgeranyltransferase I on glioma cell migration and invasion. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 6 25573158
2015 Thermodynamic mapping of effector protein interfaces with RalA and RalB. Biochemistry 6 25621740
2007 1H, 13C and 15N resonance assignments for the small G protein RalB in its active conformation. Biomolecular NMR assignments 6 19636851
1990 Chromosomal localization and cDNA sequence of human ralB, a GTP binding protein. Somatic cell and molecular genetics 6 2120779
2008 1H, 13C and 15N resonance assignments for the active conformation of the small G protein RalB in complex with its effector RLIP76. Biomolecular NMR assignments 4 19636899
1998 Immunodetection of ralA and ralB GTP-binding proteins in various rat tissues and platelets. Molecular and cellular biochemistry 4 9543348
2025 RalB uncoupling from exocyst is required for endothelial Weibel-Palade body exocytosis. Molecular biology of the cell 2 40172988
2025 Dihydroartemisinin inhibited tongue squamous cell carcinoma progression and tongue-to-lymph node metastasis through inhibiting RalB expression. Acta histochemica 2 40592008
2025 RalB promotes lymph node metastasis in tongue squamous cell carcinoma. Genes & genomics 1 40208483
2025 STAT1-mediated epigenetic regulation of LIN28A controls iPSC-derived platelet production through the let-7-RALB axis. Blood advances 1 40526838
2008 Resonance assignments for the RLIP76 Ral binding domain in its free form and in complex with the small G protein RalB. Biomolecular NMR assignments 1 19636902
2026 Chromatin-binding protein HMGN1 promotes HCC tumorigenesis via histone methylation-induced RALB transcriptional suppression. Journal of genetics and genomics = Yi chuan xue bao 0 41833635
2025 Cross-tissue transcriptome-wide association and Mendelian randomization identify RALB as a susceptibility gene for breast hypertrophy. Medicine 0 41239602
2024 RalB uncoupled exocyst mediates endothelial Weibel-Palade body exocytosis. bioRxiv : the preprint server for biology 0 39345530
2020 Retracted: microRNA-495 alleviates endothelial cell inflammatory injury in coronary heart disease via blockade of the NF-κB pathway by targeting RALB. Journal of cellular physiology 0 32810308
2008 [Preparation and characterization of monoclonal antibodies against RalB]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 18798517

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