Affinage

Showing ABL2 — ARG is a alias.

ABL2

Tyrosine-protein kinase ABL2 · UniProt P42684

Length
1182 aa
Mass
128.3 kDa
Annotated
2026-06-09
59 papers in source corpus 27 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABL2/Arg is a non-receptor tyrosine kinase that couples cell-surface receptor signaling to remodeling of the actin and microtubule cytoskeletons, thereby controlling cell migration, dendritic spine and dendrite stability, and vascular barrier integrity (PMID:18660502, PMID:23365224, PMID:33770321). The kinase is switched on by direct engagement with upstream receptors: its SH2 domain binds the integrin β1 cytoplasmic tail (with reciprocal phosphorylation of β1 Tyr-783) and phosphotyrosine Y771 of PDGFRβ, the latter triggering phosphorylation of SH3/kinase-linker tyrosines (Y116, Y161, Y272, Y310) that activate Arg kinase activity (PMID:25694433, PMID:34144039). Once active, Arg phosphorylates p190RhoGAP to inactivate RhoA and collapse the actin cytoskeleton downstream of the plexin A1/SEMA3F/NRP2 axis (PMID:18660502), while a separate C-terminal module — the (I/L)WEQ actin-binding and CH domains — directly stabilizes actin filaments, drives Arp2/3-mediated branching, and cooperates with cortactin to maintain stable filament pools (PMID:22849492, PMID:25540195). The same C-terminal half promotes microtubule nucleation and damage-site repair by forming liquid-liquid phase-separated co-condensates with tubulin (PMID:37858340). In neurons, Arg sustains dendrite arbor and dendritic spine stability through parallel RhoA-dependent and cortactin-tethering mechanisms, shaping synaptic maturation and plasticity (PMID:23365224, PMID:27335408, PMID:33622779). Beyond the cytoskeleton, Arg phosphorylates the mitochondrial protein MNRR1/CHCHD2 to stimulate respiration (PMID:27913209), and drives pro-metastatic transcriptional programs by phosphorylating TAZ and stabilizing HSF1 (PMID:31825826, PMID:33318173). Arg abundance is controlled by ubiquitin-mediated degradation, including by the F-box protein FBXO31 (PMID:42170439). A t(1;12) translocation fusing ETV6 to ABL2 implicates the kinase in human leukemia (PMID:10706884, PMID:12406085), and structural studies define how ATP-competitive and allosteric/myristate-pocket inhibitors engage its catalytic domain (PMID:21417343, PMID:25849507, PMID:40678005).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2000 Medium

    Established the first link between ABL2/ARG and human malignancy by identifying a leukemia-associated fusion that retains the full ARG kinase.

    Evidence RT-PCR cloning and sequencing of ETV6/ARG fusion transcripts from an AML-M3 cell line

    PMID:10706884 PMID:12406085

    Open questions at the time
    • Did not test the transforming activity of the fusion protein
    • Mechanism of ETV6 PNT-driven oligomerization/activation not demonstrated functionally
  2. 2008 High

    Answered how ABL2 transduces guidance-receptor signals into cytoskeletal collapse, placing it downstream of plexin A1 and upstream of RhoA.

    Evidence Co-IP, siRNA, kinase-dead mutant, and RhoA GTP/GDP activity assays with in vitro phosphorylation of p190RhoGAP

    PMID:18660502

    Open questions at the time
    • Did not resolve the structural basis of the plexin A1 interaction
    • In vivo migratory consequences not addressed
  3. 2011 High

    Provided atomic detail of the ABL2 catalytic domain bound to ATP-competitive and dual-site inhibitors, defining druggable conformations.

    Evidence X-ray co-crystal structures with imatinib, VX-680, and a triazole carbothioamide inhibitor

    PMID:21417343

    Open questions at the time
    • Structures are of the isolated kinase domain, not full-length autoregulated protein
    • No catalytic-cycle or activation-loop dynamics captured
  4. 2012 Medium

    Clarified ABL2's paradoxical role in cancer, showing it promotes invasion/metastasis while suppressing primary tumor growth and Ras-MAPK signaling.

    Evidence shRNA knockdown in breast cancer xenografts with gene-expression, invasion, and intravasation readouts

    PMID:22777352

    Open questions at the time
    • Molecular link between ABL2 and Ras-MAPK suppression not defined
    • Direct substrates driving the invasion program not identified
  5. 2012 Medium

    Identified a non-catalytic mechanism by which ABL2 enhances cortactin-actin binding through its CH domain.

    Evidence Actin co-sedimentation with Arg deletion mutants and fragments

    PMID:22849492

    Open questions at the time
    • In vitro stoichiometry not linked to a cellular phenotype here
    • Whether kinase activity modulates this binding untested
  6. 2013 High

    Dissected two distinct cytoskeletal pathways by which ABL2 stabilizes neuronal architecture — RhoA-dependent dendrite stability versus cortactin-localization-dependent spine stability.

    Evidence shRNA, RhoA inhibition, NMDAR block, and cortactin-Arg actin-binding-domain fusion rescue in hippocampal neurons

    PMID:23365224

    Open questions at the time
    • In vivo relevance addressed only in later work
    • Upstream activator in neurons not defined
  7. 2013 Medium

    Showed that endogenous ABL2 isoforms differ in localization and substrate effects, including a nuclear isoform that phosphorylates CrkII.

    Evidence Isoform transfection in COS-7, immunofluorescence, and phospho-CrkII/p190RhoGAP western blots

    PMID:23707396

    Open questions at the time
    • Overexpression may not reflect endogenous isoform stoichiometry
    • Functional significance of nuclear CrkII phosphorylation unresolved
  8. 2014 High

    Reconstituted ABL2's direct biochemical actions on actin, defining filament stabilization, Arp2/3 branch stimulation, CH-domain autoinhibition, and cofilin-severing potentiation.

    Evidence In vitro TIRF actin assembly, depolymerization, branching, and cofilin-severing assays with purified proteins and deletion mutants

    PMID:25540195

    Open questions at the time
    • How kinase signaling toggles these activities in cells not shown
    • Quantitative balance between branching and severing in vivo unknown
  9. 2015 High

    Defined the bipartite mechanism by which ABL2 directly binds and is activated by integrin β1, linking adhesion receptors to kinase activation.

    Evidence In vitro pulldowns, mutagenesis, kinase and binding assays, and cellular co-IP

    PMID:25694433

    Open questions at the time
    • Downstream substrates engaged specifically by integrin-activated ABL2 not mapped
    • Structural model of the kinase-domain/β1-tail interface absent
  10. 2015 High

    Captured the dasatinib-bound ARG catalytic domain, revealing a DFG-in conformation without activation-loop phosphorylation.

    Evidence 2.5 Å X-ray co-crystal structure of mouse ARG catalytic domain

    PMID:25849507

    Open questions at the time
    • Isolated domain only; regulatory domains not present
    • Implications for inhibitor selectivity over ABL1 not functionally tested here
  11. 2016 Medium

    Extended ABL2 substrate scope into mitochondria, showing it phosphorylates MNRR1/CHCHD2 to promote COX binding and respiration, with disease-mutant validation.

    Evidence In vitro kinase assay, co-IP, fractionation, respiration measurement, and Q112H mutant analysis

    PMID:27913209

    Open questions at the time
    • How ABL2 accesses the mitochondrial compartment not established
    • Fraction of cellular respiration controlled by this axis unquantified
  12. 2016 High

    Demonstrated in vivo that ABL2 is required for synaptic maturation, with its loss leaving immature GluN2B synapses and altered plasticity.

    Evidence Arg knockout mice with glutamate uncaging, electrophysiology, and spine morphometry

    PMID:27335408

    Open questions at the time
    • Molecular substrates linking ABL2 to GluN2B retention not identified
    • Behavioral consequences not measured here
  13. 2017 Medium

    Connected stress-hormone signaling to ABL2, showing corticosterone lowers ABL2 and substrate phosphorylation while pharmacological activation rescues dendrite and behavioral deficits.

    Evidence Western blots in cortisol-treated mice, DPH activator rescue, dendrite morphology, and behavioral tests

    PMID:29107098

    Open questions at the time
    • Mechanism by which corticosterone reduces ABL2 protein not defined
    • DPH specificity for ABL2 over ABL1 not fully controlled
  14. 2017 Medium

    Identified ABL2 as a FLT3-interacting kinase that selectively dampens AKT signaling downstream of oncogenic FLT3-ITD.

    Evidence SH2 domain array, co-IP, and Ba/F3 overexpression with phospho-signaling readouts

    PMID:28086240

    Open questions at the time
    • Mechanism of selective AKT (not ERK/p38) suppression unresolved
    • Endogenous ABL2 contribution versus overexpression untested
  15. 2018 Medium

    Localized ABL2 to ventral actin waves and adhesion foci and showed its C-terminal half, not the kinase domain, drives this recruitment and lamellipodial control.

    Evidence TIRF live imaging, Abl2 KO cells, and N/C-terminal domain complementation

    PMID:30256707

    Open questions at the time
    • Direct binding partner anchoring ABL2 to wave structures not pinpointed
    • Role of kinase activity in wave dynamics separate from recruitment unclear
  16. 2019 Medium

    Placed ABL2 in a TAZ-driven feed-forward loop required for brain metastasis, with ABL2 phosphorylating TAZ to promote its nuclear localization.

    Evidence shRNA of ABL2/AXL/TAZ, in vivo brain metastasis model, TAZ phosphorylation, and BBB-penetrant ABL inhibitor

    PMID:31825826

    Open questions at the time
    • TAZ phosphosites targeted by ABL2 not mapped
    • Generalizability beyond lung adenocarcinoma not tested
  17. 2019 Medium

    Showed ABL2 isoforms differentially program fibroblast activation and ECM remodeling, with distinct roles in adhesion versus invasion.

    Evidence Isoform rescue in Arg−/− MEFs with proliferation, migration, focal-adhesion, and ECM contraction assays

    PMID:30837227

    Open questions at the time
    • Molecular basis of isoform-specific outputs not defined
    • In vivo fibroblast relevance untested
  18. 2020 Medium

    Defined a non-catalytic ABL2 function in metastasis through direct SH3-domain binding and stabilization of HSF1, druggable by allosteric but not ATP-competitive inhibitors.

    Evidence Co-IP, SH3 binding assay, allosteric-vs-ATP-competitive inhibitor comparison, and transcriptional target measurement

    PMID:33318173

    Open questions at the time
    • Structural detail of the noncanonical SH3-HSF1 interface absent
    • How SH3 binding stabilizes HSF1 protein mechanistically unclear
  19. 2020 Medium

    Implicated ABL2 in endocytic vesicle maturation, acting downstream of EGFR to shape endocytic pits during HPV16 uptake.

    Evidence Pharmacological ABL2/EGFR inhibition with microscopy of endocytic pits and virus uptake quantification

    PMID:32188731

    Open questions at the time
    • Direct ABL2 substrates at endocytic sites not identified
    • Reliance on inhibitor specificity without genetic confirmation
  20. 2021 High

    Resolved how receptor tyrosine kinase signaling activates ABL2, mapping PDGFRβ binding to the ABL2 SH2 domain and identifying linker phosphosites whose mutation abolishes activation.

    Evidence In vitro binding/kinase assays, MS phosphosite mapping, and 4xF mutagenesis

    PMID:34144039

    Open questions at the time
    • Structural model of how linker phosphorylation relieves autoinhibition not solved
    • Cellular substrates engaged after PDGFRβ activation not profiled here
  21. 2021 High

    Established the molecular requirement for ABL2 in dendritic spine stability via a cortactin-tethered stable actin pool sustained by synaptic activity.

    Evidence GFP-actin FRAP, Abl2 shRNA, interaction mutants, and activity manipulation in hippocampal neurons

    PMID:33622779

    Open questions at the time
    • How synaptic activity drives cortactin enrichment mechanistically unresolved
    • Kinase activity requirement for stable pool maintenance not fully separated
  22. 2021 Medium

    Defined ABL2 as a regulator of endothelial barrier integrity, restraining cell spreading and adhesion through RhoA/Rac1 and contributing to inflammatory vascular leak.

    Evidence siRNA, RhoA/Rac1 activity assays, TEER, in vivo permeability assays, and patient microvessel staining

    PMID:33770321

    Open questions at the time
    • Upstream inflammatory signal activating endothelial ABL2 not identified
    • Direct substrates mediating barrier disruption not mapped
  23. 2022 Medium

    Positioned ABL2 as a degradation-controlled downstream effector of TGFβ1 signaling driving invadopodium maturation in renal cancer.

    Evidence Primary ccRCC cultures, TGFβ1 treatment, ubiquitination and 3D invasion/matrix-degradation assays

    PMID:36310399

    Open questions at the time
    • E3 ligase mediating TGFβ1/ROS-induced ABL2 degradation not identified
    • Direct invadopodial substrates of ABL2 unmapped
  24. 2023 High

    Revealed a kinase-independent ABL2 function in microtubule nucleation and repair via liquid-liquid phase separation with tubulin through its C-terminal half.

    Evidence In vitro MT dynamics reconstitution, LLPS assay, cryo-EM, and KO/domain-mutant rescue in cells

    PMID:37858340

    Open questions at the time
    • Regulation of ABL2 condensate formation in cells not defined
    • Crosstalk between MT and actin functions of the C-terminal half unresolved
  25. 2024 Medium

    Identified FBXO31 as a direct E3-ligase regulator of ABL2 abundance, linking ABL2 degradation to suppression of TNBC growth and ferroptosis resistance.

    Evidence Co-IP, ubiquitination assay, rescue experiments, ferroptosis assays, and xenografts

    PMID:42170439

    Open questions at the time
    • Degron on ABL2 recognized by FBXO31 not mapped
    • Whether this is the same axis as TGFβ1-induced degradation untested
  26. 2025 Medium

    Showed the ABL2 SH3 domain and specific myristate-pocket residues govern STAMP/allosteric inhibitor efficacy and predict distinct resistance in ABL2-rearranged leukemia.

    Evidence Truncated ZC3HAV1::ABL2 isoforms, in vitro sensitivity, in silico modeling, and in vivo mouse model

    PMID:40678005

    Open questions at the time
    • Predicted resistance mutations not yet clinically validated
    • Structural basis of ABL2-vs-ABL1 myristate-pocket selectivity inferred computationally

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ABL2's distinct outputs — RhoA inactivation, direct actin/microtubule remodeling, mitochondrial and transcriptional substrate phosphorylation — are selected and integrated by a single activated kinase in a given cellular context.
  • No unified model of context-dependent substrate selection
  • Interplay between kinase-dependent and kinase-independent (LLPS, scaffolding) functions undefined
  • Structural mechanism of full-length autoregulation unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0008092 cytoskeletal protein binding 4 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
CHCHD2CTTNFBXO31FLT3HSF1ITGB1PDGFRBPLXNA1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 ABL2/ARG directly binds plexin A1 (but not a cytoplasmic-domain-lacking plexin A1 mutant) downstream of SEMA3F/NRP2 receptor complex, then phosphorylates and activates p190RhoGAP, which inactivates RhoA (GTP→GDP), resulting in cytoskeletal collapse and inhibition of cell migration. Cells expressing an ABL2 kinase-dead mutant or treated with ABL2 siRNA failed to inactivate RhoA. Co-immunoprecipitation, siRNA knockdown, kinase-dead mutant overexpression, RhoA activity assay (GTP/GDP), in vitro phosphorylation assay The Journal of biological chemistry High 18660502
2011 Crystal structures of ABL2 kinase domain in complex with imatinib, VX-680 (tozasertib), and a type I triazole carbothioamide inhibitor were solved. Imatinib binds both the ATP-binding site of the inactive kinase and the regulatory myristate-binding site. VX-680-bound and type-I-inhibitor-bound structures reveal a DFG motif in a conformation intermediate between active and inactive states. X-ray crystallography (co-crystal structures) Journal of medicinal chemistry High 21417343
2012 Arg/Abl2 knockdown in breast cancer cells increases Ras-MAPK signaling and proliferation-associated gene expression while decreasing invasion-associated gene expression, demonstrating that Arg promotes tumor cell invasion/intravasation/metastasis in vivo while simultaneously suppressing tumor growth. shRNA knockdown in xenograft mouse model, gene expression analysis, in vivo invasion and intravasation assays Oncogene Medium 22777352
2012 Arg/Abl2 increases the stoichiometry of cortactin binding to F-actin at saturation, and the Arg C-terminal calponin homology (CH) domain is necessary and sufficient for this effect. Arg–cortactin protein–protein interactions are required for optimal cortactin–actin affinity. Actin co-sedimentation assays with Arg deletion mutants and fragments Biochemistry Medium 22849492
2013 Arg knockdown in hippocampal neurons destabilizes dendrite arbors via a RhoA-dependent mechanism, and destabilizes dendritic spines via an NMDA receptor-dependent relocalization of cortactin from spines; forcing cortactin into spines via fusion to Arg's actin-binding region prevents spine loss, demonstrating two distinct cytoskeletal control pathways for spine vs. dendrite stability. shRNA knockdown in cultured hippocampal neurons, live imaging, RhoA inhibition, NMDA receptor block, cortactin–Arg actin-binding domain fusion rescue The Journal of neuroscience High 23365224
2013 Eight full-length Arg/Abl2 isoforms are endogenously expressed in human cells; the 1BSCTS isoform has nuclear distribution and phosphorylates CrkII in the nucleus, while the other seven isoforms are cytoplasmic. Isoforms 1BLCTL, 1BSCTL, and 1ASCTS decrease stress fibers and increase p190RhoGAP phosphorylation, whereas other isoforms induce different morphological effects without reducing stress fibers. Isoform transfection in COS-7 cells, immunofluorescence localization, phospho-CrkII and phospho-p190RhoGAP western blotting Experimental cell research Medium 23707396
2014 Arg/Abl2 stabilizes actin filaments against depolymerization via its internal (I/L)WEQ actin-binding domain, stimulates Arp2/3-mediated actin branch formation (requiring the IWLEQ domain; autoinhibition by the CH domain revealed by ArgΔCH), and potentiates cofilin-mediated actin filament severing; cortactin cooperates with Arg to stabilize filaments and attenuates Arg-enhanced cofilin severing. In vitro TIRF microscopy actin assembly assays, actin depolymerization assays, branching assays with purified Arp2/3, cofilin severing assays; Arg domain deletion mutants The Journal of biological chemistry High 25540195
2015 The Arg kinase domain directly binds a lysine-rich membrane-proximal segment of the integrin β1 cytoplasmic tail; Arg phosphorylates β1 tail Tyr-783; the Arg SH2 domain then engages this phospho-Tyr-783 region; these interactions mediate direct Arg–β1 integrin binding in vitro and in cells, and activate Arg kinase activity. In vitro pulldown/binding assays, site-directed mutagenesis, in vitro kinase assay, co-immunoprecipitation from cells, kinase activity measurement The Journal of biological chemistry High 25694433
2015 Crystal structure of mouse ARG/Abl2 catalytic domain in complex with dasatinib at 2.5 Å resolution; dasatinib-bound ARG adopts a DFG-in conformation despite being non-phosphorylated on the activation-loop tyrosine, with a relatively open P-loop conformation compared to other ABL family inhibitor complexes. X-ray crystallography (co-crystal structure at 2.5 Å) Acta crystallographica. Section F, Structural biology communications High 25849507
2016 Abl2 kinase phosphorylates MNRR1 (CHCHD2) at tyrosine-99 within mitochondria; this phosphorylation promotes MNRR1 binding to cytochrome c oxidase (COX) and stimulates respiration. A disease-associated Q112H MNRR1 mutation impairs interaction with Abl2, reduces tyrosine phosphorylation, and causes defective respiration. In vitro kinase assay, co-immunoprecipitation, subcellular fractionation, respiration measurement, disease mutant analysis Biochimica et biophysica acta. Molecular cell research Medium 27913209
2016 Loss of Abl2/Arg kinase in vivo yields a subpopulation of high-release-probability, GluN2B-containing immature hippocampal synapses that persist into early adulthood; these synapses show elevated NMDA receptor currents and enlarged spine heads. As arg−/− mice age, these synapses increase in proportion coinciding with net synapse loss, and both LTP and LTD become significantly altered by P42. Arg knockout mice, focal glutamate uncaging, electrophysiology (mEPSC, LTP, LTD), immunostaining for GluN2B, morphological spine analysis The Journal of neuroscience High 27335408
2017 Corticosterone exposure reduces Abl2/Arg protein levels and phosphorylation of its substrates p190RhoGAP and cortactin in hippocampal neurons, preceding dendrite arbor atrophy; pharmacological activation of Arg kinase with a small-molecule activator (DPH) corrects dendrite arbor simplification and corticosterone-induced behavioral deficits. Western blotting for Arg and substrate phosphorylation in cortisol-treated mice, pharmacological Arg kinase activation with DPH, dendritic morphology analysis, behavioral tests Molecular and cellular neurosciences Medium 29107098
2017 ABL2 overexpression in FLT3-ITD-expressing Ba/F3 cells partially suppresses FLT3-ITD-induced proliferation and colony formation by blocking AKT phosphorylation without affecting ERK1/2 or p38, or altering FLT3 kinase activity, ubiquitination or stability. ABL2 was identified as a FLT3 interacting protein by SH2 domain array screen. SH2 domain array screen, co-immunoprecipitation, Ba/F3 cell overexpression, proliferation and colony formation assays, phospho-AKT/ERK/p38 western blotting Oncotarget Medium 28086240
2018 Abl2 localizes with cortactin at wave-like ventral actin structures at the lamellum-lamellipodium interface and at cortactin-positive foci co-localizing with integrin β3 and paxillin; the Abl2 C-terminal half (actin- and microtubule-binding domains, not the kinase domain) is necessary and sufficient for recruitment to these wave structures and for supporting normal lamellipodium size. TIRF microscopy live imaging, Abl2 knockout cells, domain complementation with N- and C-terminal Abl2 halves, immunofluorescence co-localization Molecular biology of the cell Medium 30256707
2019 The TAZ transcriptional co-activator drives expression of ABL2 and AXL in lung adenocarcinoma cells; ABL2 in turn phosphorylates TAZ to promote its nuclear localization, establishing an autocrine AXL-ABL2-TAZ feed-forward loop required for brain metastasis colonization. Knockdown of ABL2 or pharmacological inhibition with a BBB-penetrant ABL allosteric inhibitor markedly decreases brain metastases. shRNA knockdown of ABL2/AXL/TAZ, in vivo brain metastasis mouse model, TAZ phosphorylation assay, pharmacological ABL allosteric inhibitor treatment, transcriptional reporter assays Cell reports Medium 31825826
2019 The 1ALCTL and 1BLCTL Arg/Abl2 isoforms differentially regulate fibroblast activation and ECM remodeling: 1BLCTL promotes proliferation, migration/invasion, and induces a tumor-supportive milieu, while 1ALCTL maintains active focal adhesions and cell adhesion. Both isoforms support myofibroblast features including ECM contraction and stiffness. Arg isoform rescue in Arg−/− MEFs, proliferation/migration/invasion assays, focal adhesion analysis, ECM contraction assays Biology open Medium 30837227
2020 ABL2 tyrosine kinase is identified as an upstream regulator of HSF1 protein expression; the ABL2 SH3 domain directly interacts with HSF1 at a noncanonical, proline-independent SH3 interaction motif. Allosteric (but not ATP-competitive) ABL2 inhibitors disrupt this interaction and impair HSF1 protein expression and HSF1-E2F transcriptional gene targets required for brain metastasis survival. Co-immunoprecipitation, SH3 domain binding assay, pharmacological inhibitor comparison (allosteric vs ATP-competitive), shRNA knockdown, transcriptional target measurement Proceedings of the National Academy of Sciences of the United States of America Medium 33318173
2020 Abl2 acts as a regulator of endocytic vesicle maturation during HPV16 uptake; Abl2 inhibition causes accumulation of misshaped endocytic pits without reducing their number, whereas EGFR inhibition reduces pit number. Abl2 mediates downstream signaling of EGFR during HPV16 internalization, distinct from Src-mediated macropinocytosis. Pharmacological inhibition of Abl2 and EGFR, electron/fluorescence microscopy of endocytic pits, virus uptake quantification Journal of virology Medium 32188731
2021 Arg/Abl2 depletion in endothelial cells activates both RhoA and Rac1, increases cell spreading, redistributes integrin-dependent adhesions to the cell periphery, improves ECM adhesion, and reduces barrier disruption in response to inflammatory agents. In vivo, genetic Arg deletion diminishes vascular leak in skin and lungs. Arg is activated in endothelium during inflammation in murine lungs and septic patient microvessels. siRNA depletion, RhoA/Rac1 activity assays, transendothelial electrical resistance, in vivo vascular permeability assays, immunofluorescence of patient tissue Angiogenesis Medium 33770321
2021 Abl2 binding to cortactin tethers Abl2 in dendritic spines, where Abl2 and cortactin maintain a small pool of stable actin filaments required for spine stability. Disruption of Abl2:cortactin interactions by FRAP of GFP-actin eliminates the stable actin pool in spines and significantly reduces spine density. Tonic synaptic activity rescues spine loss after Abl2 depletion by promoting cortactin enrichment in spines. FRAP of GFP-actin in cultured hippocampal neurons, shRNA knockdown of Abl2, Abl2:cortactin interaction mutants, pharmacological synaptic activity manipulation The Journal of neuroscience High 33622779
2021 Abl2 SH2 domain directly binds phosphotyrosine Y771 in the PDGFRβ cytoplasmic domain; PDGFRβ directly phosphorylates novel sites on Abl2 including Y116, Y139, Y161 (SH3 domain), Y299, Y303, Y310 (kinase domain); Y116, Y161, Y272, and Y310 are at/near the SH3/SH2-kinase linker interface. PDGFRβ-mediated phosphorylation activates Abl2 kinase activity, and mutation of Y116/Y161/Y272/Y310 to Phe abrogates this activation. In vitro direct binding assay, in vitro kinase assay with mass spectrometry phosphosite mapping, site-directed mutagenesis (4xF mutant), Abl2 kinase activity measurement The Journal of biological chemistry High 34144039
2022 TGFβ1/Smad signaling and reactive oxygen species production increase ubiquitination and degradation of Abl2 protein in ccRCC cells; Abl2 promotes TGFβ1-induced ccRCC cell invasion and invadopodium maturation as a downstream effector of TGFβ1 signaling. Primary ccRCC cell cultures, TGFβ1 treatment, ubiquitination assay, 3D invasion assay, matrix degradation assay, siRNA knockdown FEBS letters Medium 36310399
2023 Abl2 promotes microtubule nucleation by undergoing liquid-liquid phase separation (LLPS) and forming co-condensates with tubulin via its C-terminal half; Abl2 binds the MT lattice adjacent to damage sites, facilitates MT repair by recruiting fresh tubulin, and increases MT rescue frequency and lifetime. The Abl2Δ688-790 isoform retains MT-lattice binding but cannot bind tubulin, promote nucleation, or increase rescue. Cryo-EM supports engagement of tubulin C-terminal tails along an extended MT lattice conformation at damage sites. MT reassembly after nocodazole washout is severely impaired in Abl2 KO cells and rescued by Abl2 but not Abl2Δ688-790. In vitro MT dynamics reconstitution (TIRF), LLPS assay, cryo-EM, Abl2 KO COS-7 cells with nocodazole washout, domain deletion mutant rescue Current biology : CB High 37858340
2025 The SH3 domain (exon 3) of Abl2 is essential for the efficacy of STAMP inhibitors (asciminib and TERN-701) targeting the Abl2 myristate pocket; different myristate pocket residues impact asciminib binding to Abl2 versus Abl1, predicting distinct resistance mutations in ABL2-rearranged ALL. Truncated ZC3HAV1::ABL2 isoforms, in vitro sensitivity assays, in silico molecular modeling, in vivo mouse model Blood neoplasia Medium 40678005
2026 FBXO31 directly interacts with ABL2 via its F-box motif and promotes ABL2 ubiquitination and proteasomal degradation, suppressing ABL2-driven TNBC cell proliferation, migration, invasion, and inhibition of xCT-mediated ferroptosis. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown rescue experiments, ferroptosis assays, mouse xenograft American journal of translational research Medium 42170439
2000 A chromosomal t(1;12)(q25;p13) translocation fuses ETV6 to ARG (ABL2), producing ETV6/ARG fusion transcripts that encode a protein containing the ETV6 PNT oligomerization domain and all functional ARG domains including the tyrosine kinase domain, identifying the first involvement of ARG in human leukemia. RT-PCR cloning of fusion transcripts, sequencing, characterization of open reading frame from AML-M3 cell line Blood Medium 10706884 12406085

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene 103 22777352
2008 ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells. The Journal of biological chemistry 93 18660502
2000 A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. Blood 86 10706884
2022 The cross-talk between Abl2 tyrosine kinase and TGFβ1 signalling modulates the invasion of clear cell Renal Cell Carcinoma cells. FEBS letters 77 36310399
2014 miR-20a promotes prostate cancer invasion and migration through targeting ABL2. Journal of cellular biochemistry 64 24464651
2013 Abl2/Arg controls dendritic spine and dendrite arbor stability via distinct cytoskeletal control pathways. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 23365224
2019 A TAZ-AXL-ABL2 Feed-Forward Signaling Axis Promotes Lung Adenocarcinoma Brain Metastasis. Cell reports 45 31825826
2015 MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2. Drug design, development and therapy 44 26766902
2015 Direct interactions with the integrin β1 cytoplasmic tail activate the Abl2/Arg kinase. The Journal of biological chemistry 36 25694433
2011 Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. Journal of medicinal chemistry 34 21417343
2014 Abl2/Abl-related gene stabilizes actin filaments, stimulates actin branching by actin-related protein 2/3 complex, and promotes actin filament severing by cofilin. The Journal of biological chemistry 33 25540195
2002 Identification of an ETV6-ABL2 fusion transcript in combination with an ETV6 point mutation in a T-cell acute lymphoblastic leukaemia cell line. British journal of haematology 31 12406085
2020 Expression differences of miR-142-5p between treatment-naïve chronic myeloid leukemia patients responding and non-responding to imatinib therapy suggest a link to oncogenic ABL2, SRI, cKIT and MCL1 signaling pathways critical for development of therapy resistance. Experimental hematology & oncology 29 32999756
2016 Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration. Biochimica et biophysica acta. Molecular cell research 28 27913209
2012 Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F-actin. Biochemistry 28 22849492
2020 The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis. Proceedings of the National Academy of Sciences of the United States of America 26 33318173
2020 Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis. Journal of virology 25 32188731
2021 Depletion of Arg/Abl2 improves endothelial cell adhesion and prevents vascular leak during inflammation. Angiogenesis 24 33770321
2016 Disruption of Coordinated Presynaptic and Postsynaptic Maturation Underlies the Defects in Hippocampal Synapse Stability and Plasticity in Abl2/Arg-Deficient Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 27335408
1989 Mapping of Abll within a conserved linkage group on distal mouse chromosome 1 syntenic with human chromosome 1 using an interspecific cross. Genomics 20 2567701
2020 Circular RNA-ABCB10 suppresses hepatocellular carcinoma progression through upregulating NRP1/ABL2 via sponging miR-340-5p/miR-452-5p. European review for medical and pharmacological sciences 19 32196586
2020 The NSs Protein Encoded by the Virulent Strain of Rift Valley Fever Virus Targets the Expression of Abl2 and the Actin Cytoskeleton of the Host, Affecting Cell Mobility, Cell Shape, and Cell-Cell Adhesion. Journal of virology 19 33087469
2021 Bone marrow mesenchymal stem cells-derived exosomal microRNA-19b-1-5p reduces proliferation and raises apoptosis of bladder cancer cells via targeting ABL2. Genomics 18 33722655
2022 Circular RNA circPGD contributes to gastric cancer progression via the sponging miR-16-5p/ABL2 axis and encodes a novel PGD-219aa protein. Cell death discovery 17 36104322
2017 Corticosteroid-induced dendrite loss and behavioral deficiencies can be blocked by activation of Abl2/Arg kinase. Molecular and cellular neurosciences 16 29107098
2018 High Expression of ABL2 Suppresses Apoptosis in Gastric Cancer. Digestive diseases and sciences 15 29767389
2014 Gleevec/imatinib, an ABL2 kinase inhibitor, protects tumor and endothelial cells from semaphorin-induced cytoskeleton collapse and loss of cell motility. Biochemical and biophysical research communications 15 24759231
2017 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. Oncotarget 12 28086240
2020 miR-143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2. The Kaohsiung journal of medical sciences 11 32196963
2024 Cancer-associated fibroblast-derived exosome Leptin promotes malignant biological lineage in pancreatic ductal adenocarcinoma by regulating ABL2 via miR-224-3p. Molecular biology reports 9 39298063
2023 ABL1 and ABL2 promote medulloblastoma leptomeningeal dissemination. Neuro-oncology advances 9 37781087
2021 Abl2:Cortactin Interactions Regulate Dendritic Spine Stability via Control of a Stable Filamentous Actin Pool. The Journal of neuroscience : the official journal of the Society for Neuroscience 9 33622779
2023 Bone mesenchymal stem cell extracellular vesicles delivered miR let-7-5p alleviate endothelial glycocalyx degradation and leakage via targeting ABL2. Cell communication and signaling : CCS 8 37587494
2023 Abl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation. Current biology : CB 8 37858340
2018 Abl2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension. Molecular biology of the cell 8 30256707
2015 Structure of the ABL2/ARG kinase in complex with dasatinib. Acta crystallographica. Section F, Structural biology communications 8 25849507
2013 One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton. Experimental cell research 8 23707396
2021 microRNA-1296 Inhibits Glioma Cell Growth by Targeting ABL2. Technology in cancer research & treatment 7 33550941
2019 The 1ALCTL and 1BLCTL isoforms of Arg/Abl2 induce fibroblast activation and extra cellular matrix remodelling differently. Biology open 7 30837227
2018 A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 6 29550892
2023 Abl2 Kinase Differentially Regulates iGluRs Current Activity and Synaptic Localization. Cellular and molecular neurobiology 5 36689065
2022 Circ_0000263 facilitates the proliferation and inhibits the apoptosis of cervical cancer depending on the regulation of miR-1179/ABL2 axis. Reproductive sciences (Thousand Oaks, Calif.) 5 35355231
2025 Activity of STAMP inhibitors in ABL2 rearranged acute lymphoblastic leukemia is dependent on the Abl2 SH3 domain. Blood neoplasia 4 40678005
2024 Long noncoding RNA LINC00858 aggravates the progression of esophageal squamous cell carcinoma via regulating the miR-425-5p/ABL2 axis. Heliyon 4 38496838
2023 The S2 Subunit of Infectious Bronchitis Virus Affects Abl2-Mediated Syncytium Formation. Viruses 4 37376546
2023 A Case Report of Infant-Type Hemispheric Glioma with a Novel GAB1-ABL2 Kinase Fusion Treated with Dasatinib. Pediatric neurosurgery 4 38109857
2021 Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation. The Journal of biological chemistry 4 34144039
2025 miR-143-3p Promotes TSCM Differentiation and Inhibits Progressive T Cell Differentiation via Inhibiting ABL2 and PAG1. Genes 2 40282426
2023 Tumor-suppressive action of miR-30a-5p in lung adenocarcinoma correlates with ABL2 inhibition and PI3K/AKT pathway inactivation. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2 37479901
2019 A Novel Case of ABL2 Chromosomal Rearrangement in High-Risk B-Cell Acute Lymphoblastic Leukemia. Journal of the Association of Genetic Technologists 2 31189154
2025 Targeting melanoma resistance: Novel oxindole and non-oxindole-based benzimidazole derivatives as potent dual inhibitors of BRAFV600E and ABL2 kinases. European journal of medicinal chemistry 1 40911967
2025 Identification of bioactive phytoconstituents as promising ABL2 inhibitors using virtual screening and molecular dynamics simulation. Scientific reports 1 41444785
2024 Impact of Abl2/Arg deficiency on anxiety and depressive behaviors in mice. Behavioural brain research 1 38697301
2024 High expression of ABL2 promotes gastric cancer cells migration, invasion and proliferation via the TGF-β and YAP signaling pathways. Journal of Cancer 1 39308677
2015 Effect of Bcl-2-siRNA on proliferation and apoptosis of pediatric acute B lymphoblastic leukemia (A-BLL) cells. Genetics and molecular research : GMR 1 26505392
2026 LncRNA DANCR promotes ABL2-mediated metastasis via decoying of miR-125a-5p in high-risk neuroblastoma. Frontiers in oncology 0 41602364
2026 Identification of a Novel, Oncogenic and Targetable TPR::ABL2 Fusion Gene in T-Cell Acute Lymphoblastic Leukaemia. EJHaem 0 41782643
2026 FBXO31-induced ABL2 ubiquitination increases cystine-glutamate antiporter-mediated ferroptosis and inhibits malignant progression in triple-negative breast cancer. American journal of translational research 0 42170439
2004 [Clonal expansion of TCR Vbeta subfamily T cells induced by bcr3-abl2 peptide]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 0 14990050

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