Affinage

ABL2

Tyrosine-protein kinase ABL2 · UniProt P42684

Length
1182 aa
Mass
128.3 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABL2 (Arg) is a cytoplasmic non-receptor tyrosine kinase that integrates receptor-initiated signals with cytoskeletal remodeling to control cell adhesion, migration, invasion, neuronal morphogenesis, and DNA repair. It signals downstream of integrin β1, EphB2, and EGFR, using its SH2/SH3 domains to engage receptors and substrates; integrin β1 directly binds and activates the Arg kinase domain, which then phosphorylates cortactin (Tyr-421), p190RhoGAP, MICAL2, Rad51, and other effectors to regulate actin dynamics, RhoA activity, invadopodium maturation, and homologous recombination (PMID:25694433, PMID:19414610, PMID:23552693, PMID:34750518, PMID:12470634). Arg possesses two C-terminal F-actin-binding domains that bundle actin filaments and cross-link them with microtubules, directly coupling its scaffolding function to adhesion-dependent lamellipodial protrusion, dendritic spine stability, and endothelial barrier integrity (PMID:11752434, PMID:15138293, PMID:23365224, PMID:33770321). In cancer, Arg drives invasion and brain metastasis through a TAZ–AXL–ABL2 feed-forward loop and an SH3-domain-mediated interaction with HSF1 that sustains an HSF1–E2F transcriptional program, while an ETV6–ARG fusion generated by chromosomal translocation is oncogenic (PMID:31825826, PMID:33318173, PMID:12080468).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Cloning of ARG established a second member of the Abelson kinase family, resolving that vertebrates encode two cytoplasmic tyrosine kinases sharing SH2/SH3/kinase architecture but with divergent C-terminal extensions.

    Evidence cDNA cloning and sequence analysis from a murine cDNA library

    PMID:2198571

    Open questions at the time
    • No kinase activity data at this stage
    • C-terminal domain functions unknown
  2. 1991 High

    Demonstration that Arg possesses intrinsic tyrosine kinase activity confirmed it as a functional kinase rather than a pseudokinase.

    Evidence Recombinant protein autokinase assay with phosphoamino acid analysis

    PMID:1923513

    Open questions at the time
    • Physiological substrates unidentified
    • Regulation of kinase activity unknown
  3. 1996 High

    Localization of Arg exclusively to the cytoplasm—unlike nuclear-targeted c-Abl—and identification of IB isoform myristoylation defined isoform-specific membrane targeting and spatial separation from Abl.

    Evidence Immunofluorescence in COS/NIH3T3 cells with [³H]myristic acid labeling and Gly-2 mutagenesis

    PMID:8700546

    Open questions at the time
    • Functional consequence of myristoylation-dependent membrane targeting not tested
    • Endogenous tissue-level localization not shown
  4. 2001 High

    Discovery that Arg bundles F-actin using two distinct actin-binding domains and identification of early substrates (Siva-1, EphB2 interaction) established Arg as both a cytoskeletal scaffold and a signal relay node.

    Evidence In vitro cosedimentation/bundling assays with domain mutants; yeast two-hybrid and Co-IP for EphB2; in vitro kinase assay for Siva-1 Tyr-48 phosphorylation

    PMID:11278261 PMID:11494128 PMID:11752434

    Open questions at the time
    • Whether bundling occurs in vivo unresolved
    • How Siva-1 phosphorylation triggers apoptosis mechanistically unclear
    • Relative contributions of kinase vs. scaffold activity not separated
  5. 2002 High

    Linking Arg to Rad51 phosphorylation and homologous recombination revealed a nuclear-independent role in genome stability, while the ETV6–ARG fusion demonstrated oncogenic potential of deregulated Arg kinase.

    Evidence Arg-knockout chicken B cells with IR sensitivity, Rad51 focus formation, and HR frequency assays; Ba/F3 IL-3 independence and Rat-1 soft-agar assays for ETV6–ARG

    PMID:12080468 PMID:12470634

    Open questions at the time
    • Which Rad51 residues are phosphorylated by Arg not mapped
    • Whether Arg enters the nucleus transiently for Rad51 phosphorylation unknown
    • ETV6–ARG in vivo leukemogenesis not tested
  6. 2004 High

    Demonstration that Arg cross-links F-actin with microtubules and that this cross-linking is required for lamellipodial dynamics in arg−/− fibroblasts unified Arg's cytoskeletal scaffolding and adhesion functions; structural EM revealed how the two actin-binding domains engage actin protomers cooperatively.

    Evidence In vitro MT-binding and F-actin/MT cross-linking reconstitution; EM image reconstruction of F-actin–Arg complexes; rescue of arg−/− fibroblast lamellipodia with domain mutants

    PMID:15138293 PMID:15670605

    Open questions at the time
    • Full-length Arg structure not determined
    • How microtubule binding is regulated in cells unknown
  7. 2005 High

    Identification that Y-261 autophosphorylation protects Arg from ubiquitination and degradation under oxidative stress revealed a self-stabilizing mechanism controlling Arg protein levels.

    Evidence Ubiquitination assays and Y-261 mutagenesis under graded H₂O₂ treatment

    PMID:15735735

    Open questions at the time
    • E3 ligase responsible for Arg ubiquitination not identified
    • Phosphatase that counteracts Y-261 unknown
  8. 2006 High

    Discovery that Arg phosphorylates proteasome subunit PSMA7 at Tyr-153 and impairs proteasome-dependent proteolysis connected Arg to cell cycle progression through proteostasis, beyond its cytoskeletal roles.

    Evidence Co-IP, in vitro kinase assay, Y153F mutagenesis with cell cycle analysis

    PMID:16678104

    Open questions at the time
    • Whether this occurs at physiological Arg expression levels unclear
    • Proteasome substrates affected not identified
  9. 2009 High

    Detailed mapping of the bidirectional Arg–cortactin interaction (SH3-mediated plus phospho-SH2-mediated) and requirement for Nck recruitment established the molecular logic of how Arg couples adhesion to cell edge protrusion.

    Evidence Reciprocal binding assays, phosphorylation mapping, rescue of Arg-deficient and cortactin-knockdown fibroblasts with interaction-defective mutants

    PMID:19414610

    Open questions at the time
    • Temporal sequence of the two binding modes in living cells not resolved
    • Whether other adapters substitute for Nck unknown
  10. 2012 High

    A suite of studies placed Arg at the center of integrin β1 signaling: direct binding of the β1 tail to Arg kinase domain activates Arg, which phosphorylates cortactin Tyr-421 for invadopodium maturation and p190RhoGAP for dendritic arbor maintenance; Arg also mediates Fcγ receptor-dependent phagocytosis in macrophages.

    Evidence Direct binding assays with integrin β1 tail; siRNA of β1 integrin with phospho-cortactin and invadopodium assays; genetic epistasis in conditional β1/arg knockout mice for dendritic phenotypes; arg−/− macrophage phagocytosis assays with in vivo Leishmania model

    PMID:22357865 PMID:22665498 PMID:23552693 PMID:25694433

    Open questions at the time
    • How β1 integrin conformational changes are transmitted to Arg activation kinetics not resolved
    • Whether Arg-dependent phagocytosis requires cortactin phosphorylation not tested
  11. 2012 High

    In vivo xenograft studies revealed that Arg promotes breast cancer invasion and metastasis while suppressing proliferation, establishing Arg as a switch between proliferative and invasive programs.

    Evidence Mouse xenograft with Arg knockdown, quantification of invasion/intravasation/metastasis, gene expression profiling

    PMID:22777352

    Open questions at the time
    • Mechanism of Ras-MAPK upregulation upon Arg loss not defined
    • Whether kinase activity or scaffold function drives invasion not separated
  12. 2013 High

    Dissection of two parallel pathways downstream of Arg in neurons—cortactin-dependent spine stabilization and p190RhoGAP-dependent dendrite maintenance—resolved how a single kinase controls morphologically distinct neuronal structures.

    Evidence Arg knockdown in hippocampal cultures with NMDA receptor blockade rescue, cortactin–actin fusion rescue, RhoA inhibitor rescue, mEPSC recordings

    PMID:23365224

    Open questions at the time
    • Whether these pathways interact or are fully independent not tested
    • In vivo behavioral consequences of Arg-dependent spine loss not assessed
  13. 2019 High

    Identification of the TAZ–AXL–ABL2 feed-forward loop in brain metastasis revealed that Arg phosphorylates transcriptional coactivator TAZ to promote its nuclear localization, creating an autocrine circuit driving metastatic colonization.

    Evidence Knockdown studies, TAZ phosphorylation and nuclear localization assays, BBB-penetrant allosteric inhibitor in vivo brain metastasis model

    PMID:31825826

    Open questions at the time
    • Specific TAZ residues phosphorylated by ABL2 not mapped
    • Whether allosteric inhibitors disrupt scaffold vs. kinase functions selectively unknown
  14. 2020 High

    Discovery that Arg's SH3 domain directly binds HSF1 through a noncanonical proline-independent motif, and that allosteric (but not ATP-competitive) inhibitors disrupt this interaction, uncovered a kinase-independent scaffolding mechanism sustaining an HSF1–E2F transcriptional program in brain-metastatic cells.

    Evidence Co-IP with domain mapping, allosteric vs. ATP-competitive inhibitor comparison, gene expression analysis upon ABL2 knockdown

    PMID:33318173

    Open questions at the time
    • Structural basis of noncanonical SH3–HSF1 binding not determined
    • Whether HSF1 interaction is relevant outside brain metastasis context unknown
  15. 2021 High

    Identification of MICAL2 as a direct Arg substrate at Tyr-445/463, with phosphorylation augmenting MICAL2-mediated F-actin disassembly, linked Arg to oxidoreductase-dependent actin regulation and HNSCC growth.

    Evidence In vitro kinase assay with MS-based phosphosite mapping, reconstituted F-actin disassembly assay, non-phosphorylatable mutant rescue in HNSCC cells

    PMID:34750518

    Open questions at the time
    • Whether MICAL2 phosphorylation occurs in non-cancer contexts unknown
    • Relative contribution of MICAL2 vs. cortactin phosphorylation to Arg-driven invasion not compared
  16. 2021 High

    Arg was established as a regulator of endothelial barrier integrity via RhoA/Rac1 control and integrin-dependent adhesion redistribution, with arg−/− mice showing reduced vascular leak, extending Arg's roles to vascular biology.

    Evidence Arg siRNA in endothelial cells with Rho GTPase activation assays and barrier function measurements; arg−/− mouse vascular leak model

    PMID:33770321

    Open questions at the time
    • Whether endothelial Arg signals through cortactin or p190RhoGAP in this context not resolved
    • Therapeutic implications of targeting Arg for vascular leak not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length autoinhibited structure of Arg, the E3 ligase mediating Arg degradation, whether kinase-independent scaffolding and kinase-dependent signaling can be genetically separated in vivo, and how Arg coordinates its diverse substrates in space and time within a single cell.
  • No full-length Arg structure available
  • E3 ubiquitin ligase for Arg unknown
  • In vivo separation of kinase vs. scaffold functions not achieved
  • Spatiotemporal substrate selectivity mechanism undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1500931 Cell-Cell communication 2 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 1
Partners
CORTACTINEPHB2HSF1ITGB1MICAL2P190RHOGAPPSMA7RAD51

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 ARG (ABL2) defines the Abelson subfamily of cytoplasmic tyrosine kinases together with c-Abl, sharing conserved tyrosine kinase, SH2, and SH3 domains and expressed as two alternative N-terminal isoforms from alternative splicing. cDNA cloning and amino acid sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 2198571
1991 The Arg protein is a 145 kDa cytoplasmic non-receptor tyrosine kinase with intrinsic autokinase (tyrosine phosphorylation) activity, widely expressed in murine tissues. Recombinant protein expression in bacteria, immune complex autokinase assay, phosphoamino acid analysis, immunoblotting of cellular protein Oncogene High 1923513
1996 Arg localizes exclusively to the cytoplasm (not nucleus), in contrast to c-Abl; the IB isoform is myristoylated at Gly-2, providing a membrane-targeting modification, while the IA isoform is not myristoylated. Indirect immunofluorescence in COS cells and NIH3T3 transfectants; [3H]myristic acid metabolic labeling; Gly-2 mutagenesis abolishing labeling Oncogene High 8700546
2001 Arg uses two distinct F-actin-binding domains (an internal domain and a C-terminal domain) to bind F-actin with positive cooperativity and to bundle F-actin in vitro; both domains are required for bundling and for inducing actin-rich structures at lamellipodia in fibroblasts. In vitro F-actin cosedimentation assays with deletion mutants, electron microscopy of bundled actin, fluorescence microscopy of Arg-YFP in Swiss 3T3 cells Proceedings of the National Academy of Sciences of the United States of America High 11752434
2001 Arg interacts with the pro-apoptotic protein Siva-1; Arg is activated by oxidative stress and phosphorylates Siva-1 on Tyr-48, potentiating Siva-1-dependent apoptosis. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (Y48 mutation), Arg-deficient cell rescue experiments The Journal of biological chemistry High 11278261
2001 Arg and Abl associate with and are reciprocally phosphorylated by EphB2 receptor; Arg SH2 domain binds to tyrosine-phosphorylated juxtamembrane motifs in EphB2, and an additional phosphorylation-independent interaction involves the C-terminal tails; activated EphB2 decreases endogenous Abl kinase activity. Yeast two-hybrid screen, co-immunoprecipitation, in vitro binding assays, kinase activity assays in cells Oncogene High 11494128
2003 Arg (and c-Abl) interact with catalase via their SH3 domains binding the P293FNP site; Arg phosphorylates catalase at Tyr-231 and Tyr-386 in vitro and in H2O2-treated cells; cells lacking both c-Abl and Arg show elevated H2O2 levels and increased H2O2-induced apoptosis. Co-immunoprecipitation, in vitro kinase assay, SH3 domain binding assay, loss-of-function in double-knockout cells The Journal of biological chemistry High 12777400
2004 Arg binds microtubules with high affinity and can cross-link F-actin bundles with microtubules in vitro; both F-actin-binding domains and the MT-binding domain are required for Arg to rescue lamellipodial dynamics in arg−/− fibroblasts adhering to fibronectin. In vitro MT-binding and F-actin/MT cross-linking assays, live imaging of lamellipodial dynamics in arg−/− fibroblasts rescued with Arg deletion mutants The Journal of cell biology High 15138293
2004 Arg modifies F-actin structure: the CH domain binds actin subdomain 1 and induces a tilt in actin protomers, while the I/LWEQ domain binds SD1 or SD4 closing the nucleotide-binding cleft; both domains cannot simultaneously bind adjacent protomers, explaining cooperative binding and bundling. Electron microscopy and single-particle image reconstruction of F-actin complexes with full-length Arg and domain deletion fragments Journal of molecular biology High 15670605
2005 Arg is ubiquitinated and degraded under high oxidative stress (1 mM H2O2), while autophosphorylation of Y-261 (or c-Abl-mediated phosphorylation of Y-261) stabilizes Arg by blocking ubiquitination and degradation. Immunoprecipitation/ubiquitination assays, site-directed mutagenesis of Y-261, protein level measurements under varying H2O2 doses Oncogene High 15735735
2006 Arg (and c-Abl) associate with and phosphorylate proteasome subunit PSMA7 (alpha4) at Tyr-153; this phosphorylation impairs proteasome-dependent proteolysis, and cells expressing PSMA7(Y153F) show impaired G1/S and S/G2 cell cycle transitions. Co-immunoprecipitation, in vitro kinase assay, phosphorylation-site mutagenesis, cell cycle analysis Molecular cell High 16678104
2007 Using a chemical genetic (bump-hole) approach, myosin IIB was identified as a direct substrate of Arg; Arg phosphorylates myosin IIB in vivo. Bump-hole chemical genetics with engineered Arg(T361A) utilizing N6-benzyl-ATP, phosphotyrosine immunopurification, mass spectrometry, in vivo validation Biochemistry Medium 17892306
2009 Arg interacts with cortactin through two mechanisms: the cortactin SH3 domain binds a proline-rich motif in the Arg C-terminus, and Arg-mediated adhesion-dependent phosphorylation of cortactin creates a binding site for the Arg SH2 domain; these interactions plus Nck adapter binding to phosphocortactin are required for adhesion-dependent cell edge protrusion. Co-immunoprecipitation, in vitro binding assays, phosphorylation assays, Arg-deficient and cortactin-knockdown fibroblasts with rescue reexpression, mutation of interaction residues The Journal of cell biology High 19414610
2011 Crystal structures of ABL2 kinase domain in complex with imatinib, tozasertib (VX-680), and a type I inhibitor reveal that imatinib binds both the ATP site of the inactive kinase and the regulatory myristate-binding site; a DFG-intermediate conformation is captured with VX-680. X-ray crystallography (co-crystal structures) Journal of medicinal chemistry High 21417343
2012 Arg phosphorylates cortactin on Tyr-421 downstream of β1 integrin activation, promoting cofilin-dependent barbed-end formation and actin polymerization required for invadopodial maturation and matrix degradation in breast cancer cells. siRNA silencing of β1 integrin, forced integrin activation, phospho-specific antibodies, invadopodium formation and matrix degradation assays in 2D and 3D matrices Molecular biology of the cell High 23552693
2012 The intracellular tail of integrin β1 binds directly to Arg kinase; this interaction stimulates Arg-dependent activation of p190RhoGAP (which inactivates RhoA), and genetic reduction of integrin β1–Arg signaling recapitulates integrin β1 knockout phenotypes in hippocampal neurons (reduced dendritic arbors, synapse loss). Direct binding assays (integrin β1 tail–Arg interaction), biochemical activation assay of p190RhoGAP, genetic epistasis in conditional integrin β1 and arg knockout mice The Journal of neuroscience High 22357865
2012 Arg promotes breast cancer cell invasion, intravasation, and lung metastasis in vivo while simultaneously suppressing tumor cell proliferation; Arg knockdown upregulates Ras-MAPK signaling and proliferation genes while downregulating invasion genes. Mouse xenograft model with Arg knockdown, quantification of invasion/intravasation/metastasis, gene expression and signaling pathway analysis Oncogene High 22777352
2012 Arg modulates the stoichiometry and affinity of cortactin binding to F-actin; the Arg C-terminal calponin homology domain is necessary and sufficient to increase cortactin–F-actin binding stoichiometry. Actin cosedimentation assays with Arg deletion mutants and cortactin, quantitative binding analysis Biochemistry High 22849492
2012 Arg mediates IgG-opsonized (Fc receptor-dependent) phagocytosis in macrophages; Arg-deficient macrophages are specifically defective in IgG1-opsonized Leishmania amastigote uptake but not C3bi-coated bead phagocytosis. Arg-deficient macrophages, imatinib inhibition, phagocytosis assays with differentially opsonized beads and parasites, in vivo murine leishmaniasis model Molecular and cellular biology High 22665498
2013 Arg controls dendritic spine stability through dampening NMDA receptor-dependent relocalization of cortactin from spines (actin stabilization pathway), while dendrite arbor stability is maintained separately through attenuation of RhoA activity via p190RhoGAP. Arg knockdown in hippocampal neuronal cultures, NMDA receptor blockade rescue, cortactin–actin fusion rescue, RhoA inhibitor rescue, miniature EPSC recordings The Journal of neuroscience High 23365224
2014 miR-20a directly targets ABL2 and negatively regulates ABL2-dependent phosphorylation of p190RhoGAP; ABL2 knockdown promotes prostate cancer cell invasion and migration. Luciferase reporter assay confirming miR-20a targeting of ABL2 3'UTR, Western blotting, transwell invasion/migration assays, rescue experiments Journal of cellular biochemistry Medium 24464651
2015 The Arg kinase domain directly interacts with a lysine-rich membrane-proximal segment of the integrin β1 cytoplasmic tail; Arg phosphorylates β1 tail Tyr-783; the Arg SH2 domain then engages the phosphorylated tail; these interactions activate Arg kinase activity. In vitro direct binding assays (recombinant proteins), in vitro kinase assay, co-immunoprecipitation in cells, Arg kinase activation assay The Journal of biological chemistry High 25694433
2016 Src family kinases Hck, Fgr, and Lyn activate Arg to facilitate IgG-mediated (Fc receptor) phagocytosis and Leishmania amastigote uptake by macrophages; Src-mediated Arg activation is required for efficient uptake. Small molecule inhibitors, primary macrophages lacking specific Src kinases, Arg activation assays, phagocytosis assays, in vivo Leishmania infection model with bosutinib treatment Journal of cell science High 27358479
2017 Optogenetic activation of EphB2 in dendrites induces rapid actin polymerization and dendritic filopodial growth in hippocampal neurons; Abl2/Arg is identified as a necessary effector downstream of EphB2 in this process (Rac1 and CDC42 are not required). Optogenetic OptoEphB2 photoactivation in hippocampal neurons, Arg inhibitor treatment, live actin imaging Biology open Medium 29158322
2017 ABL2 interacts with FLT3-ITD (oncogenic mutant FLT3) via SH2 domain array binding and suppresses FLT3-ITD-induced cell proliferation and colony formation by partially blocking FLT3-induced AKT phosphorylation without affecting ERK1/2 or p38. SH2 domain array screen, co-immunoprecipitation in Ba/F3 cells, proliferation/colony assays with ABL2 overexpression, phospho-specific immunoblotting Oncotarget Medium 28086240
2018 Abl/Arg promote secretion of cathepsin B and cathepsin L in melanoma by activating transcription factors Ets1, Sp1, and NF-κB/p65; in some cell lines this occurs in a kinase-independent manner while in others it is kinase-dependent; cathepsin secretion is required for Abl/Arg-driven invasion in vitro and metastasis in vivo. Abl/Arg kinase inhibitors, kinase-dead mutants, transcription factor knockdowns, cathepsin secretion assays, invasion assays, in vivo metastasis model Science signaling High 29463776
2019 ABL2 participates in an autocrine TAZ-AXL-ABL2 feed-forward signaling loop required for lung adenocarcinoma brain metastasis: TAZ drives ABL2 and AXL expression, ABL2 in turn phosphorylates TAZ promoting its nuclear localization; allosteric ABL2 inhibition or ABL2/AXL/TAZ knockdown markedly reduces brain metastases. Knockdown studies, TAZ phosphorylation assays, nuclear localization assays, BBB-penetrant allosteric inhibitor treatment, in vivo brain metastasis model Cell reports High 31825826
2020 ABL2 SH3 domain directly interacts with HSF1 protein at a noncanonical, proline-independent SH3 interaction motif; ABL2 regulates HSF1 protein expression and an HSF1-E2F transcriptional program required for brain-metastatic lung cancer cell survival; allosteric (but not ATP-competitive) ABL2 inhibitors disrupt this interaction. Co-immunoprecipitation, domain mapping, allosteric vs. ATP-competitive inhibitor comparison, ABL2 knockdown and pharmacologic inhibition, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 33318173
2020 Abl2/Arg mediates CXCL12/CXCR4-induced glioma cell invadopodia formation and invasion through cortactin phosphorylation; Arg interacts with cortactin in glioma cells and its silencing blocks CXCL12-driven invasion. Co-immunoprecipitation of Arg and cortactin, Arg siRNA knockdown, invadopodium formation assays, phospho-cortactin immunoblotting, invasion assays Experimental cell research Medium 32035133
2020 Abl2 regulates endocytic vesicle maturation during HPV16 uptake downstream of EGFR; Abl2 inhibition causes accumulation of misshaped endocytic pits, indicating a role in endocytic pit scission/maturation rather than pit induction. Abl2-specific inhibitors, electron microscopy of endocytic pits, HPV16 internalization assays, epistasis with EGFR inhibitors Journal of virology Medium 32188731
2021 Arg/Abl2 is a central regulator of endothelial barrier integrity; Arg depletion activates RhoA and Rac1, redistributes integrin-dependent adhesions, and reduces adherens junction disruption and intercellular gap formation; genetic deletion of Arg reduces vascular leak in vivo. Arg siRNA depletion in endothelial cells, RhoA/Rac1 activation assays, cell spreading and adhesion measurements, barrier function assays, arg−/− mouse vascular leak model Angiogenesis High 33770321
2021 ARG kinase phosphorylates MICAL2 at Tyr-445 and Tyr-463 (confirmed by direct phosphorylation assay and mass spectrometry); these phosphorylations augment MICAL2-mediated F-actin disassembly and promote HNSCC growth and invasion; non-phosphorylatable MICAL2 mutants (Y445F, Y463F) fail to rescue HNSCC proliferation. Co-immunoprecipitation, in vitro kinase assay with mass spectrometry identification of phosphosites, F-actin disassembly assay with purified recombinant proteins, non-phosphorylatable mutant rescue experiments Oncogene High 34750518
2002 ETV6/ARG fusion kinase (ARG kinase domain fused to ETV6 HLH oligomerization domain) is oncogenic: it confers IL-3-independent growth to Ba/F3 cells and anchorage-independent growth to Rat-1 fibroblasts, and activates PI3K, SHC, Ras-GAP, and CRK-L signaling; the ETV6 HLH domain is required for oncogenic activity. Stable expression in Ba/F3 and Rat-1 cells, IL-3 independence assays, soft-agar colony assays, phosphotyrosine immunoblotting of signaling molecules, domain deletion analysis Oncogene High 12080468
2002 Arg interacts with and phosphorylates Rad51 in cells; Arg-deficient cells show reduced IR-induced Rad51 focus formation, hypersensitivity to ionizing radiation, elevated chromosomal aberrations, and reduced homologous recombination frequencies, indicating Arg functions in homologous recombinational DNA repair. Co-immunoprecipitation, in vitro kinase assay, targeted gene disruption in chicken B cells, IR survival assays, Rad51 immunofluorescence, chromosomal aberration analysis, gene targeting frequency measurement Biochemical and biophysical research communications High 12470634

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases. Proceedings of the National Academy of Sciences of the United States of America 151 2198571
2003 Catalase activity is regulated by c-Abl and Arg in the oxidative stress response. The Journal of biological chemistry 150 12777400
1992 Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proceedings of the National Academy of Sciences of the United States of America 137 1502149
2008 Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis. The Journal of biological chemistry 127 18499678
2013 β1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. Molecular biology of the cell 118 23552693
2012 Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene 103 22777352
2002 Novel fibrinogen gamma375 Arg-->Trp mutation (fibrinogen aguadilla) causes hepatic endoplasmic reticulum storage and hypofibrinogenemia. Hepatology (Baltimore, Md.) 103 12198657
1991 An Arg-Gly-Asp sequence within thrombin promotes endothelial cell adhesion. The Journal of cell biology 102 1988465
2012 Integrin β1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 22357865
2001 The Abl-related gene (Arg) nonreceptor tyrosine kinase uses two F-actin-binding domains to bundle F-actin. Proceedings of the National Academy of Sciences of the United States of America 94 11752434
2009 Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. The Journal of cell biology 87 19414610
2006 Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg. Journal of controlled release : official journal of the Controlled Release Society 87 16842881
2004 The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. The Journal of cell biology 83 15138293
2012 Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 22396406
1992 The Ser-Arg-Tyr-Asp region of the major surface glycoprotein of Leishmania mimics the Arg-Gly-Asp-Ser cell attachment region of fibronectin. The Journal of biological chemistry 73 1629196
2001 Multiple signaling interactions of Abl and Arg kinases with the EphB2 receptor. Oncogene 70 11494128
2005 Indole alkaloids from Tabernaemontana australis (Muell. Arg) Miers that inhibit acetylcholinesterase enzyme. Bioorganic & medicinal chemistry 69 15911323
2000 A novel pro-Arg motif recognized by WW domains. The Journal of biological chemistry 69 10744724
2014 miR-20a promotes prostate cancer invasion and migration through targeting ABL2. Journal of cellular biochemistry 64 24464651
2016 Molecular Recognition of Lys and Arg Methylation. ACS chemical biology 63 26759915
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
2001 The ARG tyrosine kinase interacts with Siva-1 in the apoptotic response to oxidative stress. The Journal of biological chemistry 55 11278261
2006 Interaction between c-Abl and Arg tyrosine kinases and proteasome subunit PSMA7 regulates proteasome degradation. Molecular cell 48 16678104
1998 Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with an Arg-Pro-Arg positive patch. Chemistry & biology 47 9545429
2010 The soluble form of urokinase receptor promotes angiogenesis through its Ser⁸⁸-Arg-Ser-Arg-Tyr⁹² chemotactic sequence. Journal of thrombosis and haemostasis : JTH 46 20880257
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
2001 The susceptibility of Mycobacterium tuberculosis to isoniazid and the Arg-->Leu mutation at codon 463 of katG are not associated. Journal of clinical microbiology 42 11283093
2004 Ni(II).Arg-Gly-His-DNA interactions: investigation into the basis for minor-groove binding and recognition. Journal of the American Chemical Society 40 15113212
1991 Arg encodes a widely expressed 145 kDa protein-tyrosine kinase. Oncogene 40 1923513
2002 Roles for Arg- and Lys-gingipains in the disruption of cytokine responses and loss of viability of human endothelial cells by Porphyromonas gingivalis infection. Biological chemistry 39 12437109
2018 Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis. Science signaling 38 29463776
1990 Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A. Blood 38 2104766
2012 The Abl and Arg kinases mediate distinct modes of phagocytosis and are required for maximal Leishmania infection. Molecular and cellular biology 37 22665498
1996 Subcellular localization of the Arg protein tyrosine kinase. Oncogene 37 8700546
2015 Direct interactions with the integrin β1 cytoplasmic tail activate the Abl2/Arg kinase. The Journal of biological chemistry 36 25694433
2023 Tackling Soil ARG-Carrying Pathogens with Global-Scale Metagenomics. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 35 37424042
2019 Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: An Antiviral Compound That Acts against Flaviviruses through the Inhibition of Furin-Mediated prM Cleavage. Viruses 35 31683742
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
1997 Apolipoprotein A-IFIN (Leu159-->Arg) mutation affects lecithin cholesterol acyltransferase activation and subclass distribution of HDL but not cholesterol efflux from fibroblasts. Arteriosclerosis, thrombosis, and vascular biology 34 9409289
2014 Mallotus philippinensis Muell. Arg (Euphorbiaceae): ethnopharmacology and phytochemistry review. BioMed research international 32 25105119
1988 Renal autoimmune epitope of group A streptococci specified by M protein tetrapeptide Ile-Arg-Leu-Arg. Proceedings of the National Academy of Sciences of the United States of America 32 2454473
2001 Involvement of the Arg-Asp-His catalytic triad in enzymatic cleavage of the phosphodiester bond. Biochemistry 31 11331006
2012 Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). Journal of ethnopharmacology 30 22301443
2003 Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombin. American journal of physiology. Heart and circulatory physiology 30 12598231
2016 The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection. Journal of cell science 29 27358479
2012 Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F-actin. Biochemistry 28 22849492
1993 Importance of Arg-219 for correct biogenesis of alpha 1 homooligomeric glycine receptors. FEBS letters 28 7506679
2023 Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2. Nature cell biology 27 37059883
1996 Isolation and analysis of the arg-13 gene of Neurospora crassa. Genetics 27 8807290
1995 Methionine-enkephalin-Arg-Phe immunoreactivity in heart tissue. Peptides 27 8545242
2020 tRNAArg-Derived Fragments Can Serve as Arginine Donors for Protein Arginylation. Cell chemical biology 26 32553119
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
2014 Structures of Arg- and Gln-type bacterial cysteine dioxygenase homologs. Protein science : a publication of the Protein Society 26 25307852
2004 Characterization of a pseudoachondroplasia-associated mutation (His587-->Arg) in the C-terminal, collagen-binding domain of cartilage oligomeric matrix protein (COMP). The Biochemical journal 26 14580238
1999 Identification of a novel Arg-->Cys mutation in the LDL receptor that contributes to spontaneous hypercholesterolemia in pigs. Journal of lipid research 26 10064736
2020 Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis. Journal of virology 25 32188731
2015 Cyclization of the urokinase receptor-derived ser-arg-ser-arg-tyr Peptide generates a potent inhibitor of trans-endothelial migration of monocytes. PloS one 25 25938482
2021 Depletion of Arg/Abl2 improves endothelial cell adhesion and prevents vascular leak during inflammation. Angiogenesis 23 33770321
2020 Arg kinase mediates CXCL12/CXCR4-induced invadopodia formation and invasion of glioma cells. Experimental cell research 23 32035133
2004 The Arg non-receptor tyrosine kinase modifies F-actin structure. Journal of molecular biology 23 15670605
2004 Does a Leu 512 Arg thyrotropin receptor mutation cause an autonomously functioning papillary carcinoma? Thyroid : official journal of the American Thyroid Association 23 15671779
2010 Oxytocin-Gly-Lys-Arg: a novel cardiomyogenic peptide. PloS one 22 21048978
2001 Identification of a missense mutation (G329A;Arg(110)--> GLN) in the human FUT7 gene. The Journal of biological chemistry 22 11404359
2009 p53 methylation--the Arg-ument is clear. Cell cycle (Georgetown, Tex.) 21 19221494
2009 Modeling of tRNA-assisted mechanism of Arg activation based on a structure of Arg-tRNA synthetase, tRNA, and an ATP analog (ANP). The FEBS journal 21 19656186
2005 Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress. Oncogene 21 15735735
2020 Arg-GlcNAcylation on TRADD by NleB and SseK1 Is Crucial for Bacterial Pathogenesis. Frontiers in cell and developmental biology 20 32766249
2017 Investigating Liquid-Liquid Phase Separation of a Monoclonal Antibody Using Solution-State NMR Spectroscopy: Effect of Arg·Glu and Arg·HCl. Molecular pharmaceutics 20 28614662
2017 Optogenetic activation of EphB2 receptor in dendrites induced actin polymerization by activating Arg kinase. Biology open 20 29158322
2004 Inter-nerves and intra-nerve conduction heterogeneity in CMTX with Arg(15)Gln mutation. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 20 14706470
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
2005 NahR: effects of replacements at Asn 169 and Arg 248 on promoter binding and inducer recognition. Archives of biochemistry and biophysics 19 15629110
2004 Arg and DAP3 expression was correlated with human thymoma stage. Clinical & experimental metastasis 19 15679048
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
2007 Polymorphism of XRCC1 codon arg 399 Gln is associated with higher susceptibility to endometriosis. The Chinese journal of physiology 18 18442016
2002 Transformation of Ba/F3 cells and Rat-1 cells by ETV6/ARG. Oncogene 18 12080468
2020 The Arg/N-degron pathway targets transcription factors and regulates specific genes. Proceedings of the National Academy of Sciences of the United States of America 17 33229537
1989 Inflammatory properties of human C5a and C5a des Arg/ in mast cell-depleted human skin. The Journal of investigative dermatology 17 2527912
2009 Alpha-fetoprotein related gene (ARG): a new member of the albumin gene family that is no longer functional in primates. Gene 16 19733224
1994 Fibrinogen Milano V: a congenital dysfibrinogenaemia with a gamma 275 Arg-->Cys substitution. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 16 7841300
2019 Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics. Acta crystallographica. Section D, Structural biology 15 31205020
2018 A Strategically Located Arg/Lys Residue Promotes Correct Base Paring During Nucleic Acid Biosynthesis in Polymerases. Journal of the American Chemical Society 15 29424536
2018 High Expression of ABL2 Suppresses Apoptosis in Gastric Cancer. Digestive diseases and sciences 15 29767389
2014 Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children. Molecular genetics and metabolism 15 25087164
1999 Arg-gly-Asp (RGD) peptides and peptidomimetics as therapeutics: relevance for renal diseases. Experimental nephrology 15 10213871
2023 Rhizosphere suppression hinders antibiotic resistance gene (ARG) spread under bacterial invasion. One health (Amsterdam, Netherlands) 14 36683960
2009 Utilization of Arg-elution method for FLAG-tag based chromatography. Protein expression and purification 14 19362151
2002 Arg tyrosine kinase is involved in homologous recombinational DNA repair. Biochemical and biophysical research communications 14 12470634
2007 Use of a chemical genetic technique to identify myosin IIb as a substrate of the Abl-related gene (Arg) tyrosine kinase. Biochemistry 13 17892306
2006 Residues His-15 and Arg-17 of HPr participate differently in catabolite signal processing via CcpA. The Journal of biological chemistry 13 17085448
1995 Isolation and characterization of the arginase-encoding gene (arg) from Coccidioides immitis. Gene 13 7867937
2021 Phosphorylation of MICAL2 by ARG promotes head and neck cancer tumorigenesis by regulating skeletal rearrangement. Oncogene 12 34750518
2020 De Novo Resistance to Arg10-Teixobactin Occurs Slowly and Is Costly. Antimicrobial agents and chemotherapy 12 33046494
2017 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. Oncotarget 12 28086240
2014 Contribution of cationic amino acids toward the inhibition of Arg-specific cysteine proteinase (Arg-gingipain) by the antimicrobial dodecapeptide, CL(14-25), from rice protein. Biopolymers 12 25046435
2020 miR-143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2. The Kaohsiung journal of medical sciences 11 32196963
2017 The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg-Gly-Asp motif. The Journal of biological chemistry 11 28882889
1988 Complement C5a receptor antagonism by protamine and poly-L-Arg on human leukocytes. Complement (Basel, Switzerland) 11 3180741