Affinage

WAS

Mitochondrial-derived peptide MOTS-c · UniProt A0A0C5B5G6

Length
16 aa
Mass
2.2 kDa
Annotated
2026-06-11
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WAS encodes WASP, a hematopoietic actin nucleation-promoting factor that couples upstream GTPase and tyrosine-kinase signals to Arp2/3-dependent actin assembly (PMID:9422512). Activation is governed by relief of VCA-domain autoinhibition followed by dimerization/oligomerization that raises Arp2/3 affinity up to 180-fold (PMID:18995840); Cdc42 reverses autoinhibition and cooperates synergistically with the Src-family kinase Lck to stimulate phosphorylated WASP (PMID:9422512, PMID:16293614), and Cdc42 is a more effective WASP activator than is the case for the N-WASP paralog, which is preferentially driven by Rac1 and PIP2 (PMID:17302440). WASP is engaged by Src-family kinases through SH3–proline-rich interactions (PMID:8805332), with Hck serving as the dominant WASP-phosphorylating kinase in macrophages where it controls phagocytosis, chemotaxis, podosome dynamics, and matrix degradation (PMID:24482227). WASP stability is enforced by constitutive binding to WIP, which shields it from calpain- and proteasome-mediated degradation (PMID:17213309), while tyrosine phosphorylation of WIP releases WASP and triggers its rapid degradation and podosome loss (PMID:25413351); WASP activity is terminated by Y291-phosphorylation-dependent recruitment of the E3 ligases Cbl-b and c-Cbl, which ubiquitylate K76/K81 in the WH1 domain (PMID:22665495). Through these mechanisms WASP drives immunological synapse reformation (PMID:17512410), topology-directed neutrophil migration and front-rear polarity via Cdc42-biased Arp2/3 recruitment (PMID:34964841), lysosome actin-comet motility (PMID:17500055), and T- and B-cell development (PMID:17878299, PMID:22411869). Gain-of-function mutations producing a constitutively open, membrane-localized WASP cause X-linked neutropenia with hyperactive neutrophils (PMID:30124469), and loss of WASP/WIP acts as a tumor suppressor lesion in T-cell lymphoma through elevated CDC42-GTP (PMID:30510251).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Established WASP as a physical effector of Src-family tyrosine kinase signaling, linking it to receptor-proximal kinase cascades in hematopoietic cells.

    Evidence GST-SH3 affinity chromatography and co-immunoprecipitation in haematopoietic cells, principally with Fyn

    PMID:8805332

    Open questions at the time
    • Did not define the functional consequence of phosphorylation on actin output
    • Did not distinguish which kinase is dominant in which cell type
  2. 1998 High

    Defined the core output mechanism: WASP's VCA domain transmits Cdc42 GTPase signals to Arp2/3-driven actin polymerization.

    Evidence Cell-free actin depolymerization assays, cellular co-expression, and domain analysis of WASP/N-WASP

    PMID:9422512

    Open questions at the time
    • Did not quantify the affinity gains underlying activation
    • Did not address dimerization or cell-type-specific regulation
  3. 2001 Medium

    Identified WASP as a calpain substrate, proposing a Ca2+-dependent proteolytic switch terminating actin-driven projections, distinguishing it from N-WASP.

    Evidence Ex vivo broken-cell calpain cleavage assays with calpeptin/E64d inhibitors in stimulated platelets

    PMID:11698281

    Open questions at the time
    • Single-lab biochemical assay without in vivo confirmation of the switch
    • Cleavage sites not mapped
  4. 2005 High

    Resolved how two upstream inputs are integrated, showing Cdc42 and Lck cooperate synergistically and quantifying the coupling energy of WASP activation.

    Evidence In vitro kinase and actin polymerization assays with purified proteins and kinetic analysis

    PMID:16293614

    Open questions at the time
    • In vitro coupling energetics not validated in cells
    • Did not address downstream termination
  5. 2007 High

    Established WIP as an obligate WASP chaperone, explaining why WASP protein collapses without WIP and defining a degradation axis via calpain and proteasome.

    Evidence WIP-knockout T cells, proteasome/calpain inhibitors, WASP protein quantification, and WIP domain mapping; NMR structure of the WIP-EVH1 interface

    PMID:17205972 PMID:17213309 PMID:17229736

    Open questions at the time
    • Minimal WIP WASP-binding domain insufficient to restore WASP-dependent IL-2 transcription
    • Did not define the signal that releases WASP from WIP
  6. 2007 High

    Distinguished WASP from N-WASP by their differential GTPase and lipid responsiveness, showing the paralogs are not interchangeable in their upstream wiring.

    Evidence In vitro pyrene actin nucleation assays with purified full-length WASP and N-WASP and multiple activators

    PMID:17302440

    Open questions at the time
    • Single-lab in vitro comparison
    • Did not test combinatorial activator inputs in cells
  7. 2007 High

    Assigned WASP a specific cellular task in T cells — reforming the immunological synapse after migration — in opposition to PKCtheta-driven symmetry breaking.

    Evidence WASp-/- and PKCtheta-/- T cell live imaging in vitro and in vivo with double-mutant epistasis

    PMID:17512410

    Open questions at the time
    • Molecular link between WASP actin activity and synapse stability not detailed
    • Did not connect to the WIP/ubiquitylation regulatory layers
  8. 2007 High

    Extended WASP function to organelle dynamics, showing Hck-triggered, Cdc42-dependent WASP/Arp2/3 actin comet tails propel lysosomes.

    Evidence In vitro actin comet reconstitution on lysosomes and beads with WASP-/- cells, Arp2/3 inhibition, and GTPase inhibitors

    PMID:17500055

    Open questions at the time
    • In vivo physiological role of lysosome comets not established
    • Did not address other organelle substrates
  9. 2007 High

    Demonstrated functional redundancy between WASP and N-WASP in T-cell development, revealing combined requirement masked in single knockouts.

    Evidence RAG2 blastocyst complementation and conditional Cre-loxP double knockout with flow cytometry and migration assays

    PMID:17878299

    Open questions at the time
    • Stage-specific molecular targets of the actin defect not defined
    • Relative contribution of each paralog per developmental step unresolved
  10. 2008 High

    Refined the activation model by showing WASP uses two hierarchical mechanisms — autoinhibition relief plus dimerization that boosts Arp2/3 affinity up to 180-fold — unifying diverse activators.

    Evidence In vitro actin assembly, dimerization, and affinity measurements with mechanistic mutagenesis

    PMID:18995840

    Open questions at the time
    • In vivo prevalence of dimeric versus monomeric WASP not measured
    • Did not specify which physiological ligands drive dimerization in cells
  11. 2012 High

    Identified the termination switch: Y291 phosphorylation recruits Cbl-b/c-Cbl to ubiquitylate WASP at K76/K81, controlling WASP turnover and actin dynamics after TCR engagement.

    Evidence TCR-stimulated T cells, ubiquitylation assays, K76/K81 and Y291 mutagenesis, and Cbl co-immunoprecipitation

    PMID:22665495

    Open questions at the time
    • Interplay between Cbl-mediated degradation and WIP-mediated protection not resolved
    • Did not quantify how much active WASP this removes physiologically
  12. 2012 High

    Showed WASP/N-WASP are also jointly required for peripheral B-cell development, spreading, antigen uptake, and antibody responses, broadening the actin requirement across lymphocyte lineages.

    Evidence Conditional B-cell double knockout mice with spreading, homing, antigen uptake, and antibody response assays

    PMID:22411869

    Open questions at the time
    • Molecular distinction between development and migration defects not mapped
    • Did not identify the receptor inputs driving each phenotype
  13. 2014 High

    Named Hck as the primary WASP-phosphorylating kinase in macrophages, tying WASP phosphorylation to phagocytosis, podosomes, and matrix degradation.

    Evidence Hck-/- macrophages and siRNA knockdown with phagocytosis, chemotaxis, and matrix degradation assays under CX3CL1/FcgR stimulation

    PMID:24482227

    Open questions at the time
    • Phosphorylated tyrosine residues not individually mapped here
    • Redundancy with other Src-family kinases in macrophages not excluded
  14. 2014 High

    Linked WIP phosphorylation to WASP release and degradation, showing Btk-dependent WIP tyrosine phosphorylation destabilizes WASP and disrupts podosomes.

    Evidence WIP knockdown with phosphomimic rescue, WASP stability and podosome assays, and a kinase-inhibitor screen identifying Btk

    PMID:25413351

    Open questions at the time
    • Direct Btk-WIP phosphorylation not biochemically reconstituted
    • Coordination with Cbl-mediated WASP ubiquitylation unresolved
  15. 2016 High

    Assigned a cell-intrinsic immunoregulatory role to WASP in Tregs, showing Treg-specific WASP is required to restrain Th2 responses and prevent food allergy.

    Evidence FOXP3-conditional Was knockout versus global knockout with cytokine profiling, GATA3 analysis, and germ-free controls

    PMID:27643438

    Open questions at the time
    • Mechanistic link between actin regulation and GATA3/Th2 restraint not defined
    • Did not identify the molecular pathway downstream of WASP in Tregs
  16. 2016 High

    Demonstrated conserved signaling logic in C. elegans, placing WASP downstream of MIG-13/SEM-5(Grb2) with cooperative activation by SEM-5 and MIG-2 during neuroblast migration.

    Evidence C. elegans genetics, GFP knockin, in vitro F-actin branching with purified proteins, and WAVE epistasis

    PMID:27780040

    Open questions at the time
    • Mammalian relevance of the Grb2-WASP axis not tested
    • Degree of WASP/WAVE compensation not quantified
  17. 2018 High

    Defined the molecular basis of X-linked neutropenia: gain-of-function mutations produce constitutively open, membrane-localized WASP that is PI3K-independent and hyperactivates actin dynamics.

    Evidence XLN patient neutrophils and two mouse models with conformation, phosphorylation, and actin-dynamics analysis under PI3K inhibition

    PMID:30124469

    Open questions at the time
    • Long-term consequences of constitutive activation on hematopoiesis not detailed
    • Relationship to Y291/Y293 termination signaling not fully integrated
  18. 2018 High

    Established WASP/WIP as tumor suppressors in T-cell lymphoma acting by restraining CDC42-GTP, with ALK-STAT3-C/EBPbeta suppressing their expression.

    Evidence WASP/WIP-deficient mice, CDC42-GTP pulldown, CDC42 heterozygous rescue, and ALK inhibitor experiments

    PMID:30510251

    Open questions at the time
    • Mechanism linking WASP loss to CDC42-GTP accumulation not fully defined
    • Human ALCL therapeutic relevance not directly tested
  19. 2019 Medium

    Showed WASP maintains front-rear polarity by restricting active Rac to the cell front through its CRIB motif, separable from its Arp2/3 and endocytic functions.

    Evidence Dictyostelium WASP knockout, CRIB mutants, FRET Rac reporters, and endocytosis assays

    PMID:31786060

    Open questions at the time
    • Demonstrated in Dictyostelium, not mammalian cells
    • Mechanism by which CRIB restricts Rac not molecularly defined
  20. 2021 High

    Linked WASP to mechanosensing, showing it enriches at substrate-induced membrane invagination necks in a Cdc42-biased manner to direct topology-guided neutrophil migration.

    Evidence WASP-knockout neutrophils with superresolution and live imaging on 3D substrates and Arp2/3 localization assays

    PMID:34964841

    Open questions at the time
    • Sensor that couples membrane curvature to WASP recruitment not identified
    • In vivo contribution to tissue migration not measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the protective (WIP), terminating (Cbl ubiquitylation, calpain, WIP phosphorylation) and activating (Cdc42/kinase/dimerization) layers are temporally coordinated at a single actin structure remains unresolved.
  • No integrated kinetic model of WASP lifecycle from activation to degradation
  • Cell-type-specific balance of these regulators not mapped
  • Structural state of WASP during dimerization in cells not directly observed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1643685 Disease 2
Partners
ABI1CBLCBLBCDC42FYNHCKLCKWIPF1
Complex memberships
Arp2/3 complex (activator)WIP-WASP complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 WASP (and its homolog N-WASP) contains a VCA domain that links upstream signals including Cdc42 (Rho GTPase) to activation of the Arp2/3 complex, leading to actin polymerization; Cdc42 binds WASP/N-WASP to regulate actin dynamics and filopodium formation. Cell-free system actin depolymerization assay, co-expression in cells, functional domain analysis Nature High 9422512
1996 WASP physically associates with c-Src family protein-tyrosine kinases, particularly Fyn, through SH3 domain-proline-rich region interactions; this interaction was demonstrated both in vitro (affinity chromatography with GST-SH3 fusion proteins) and in vivo (co-immunoprecipitation in human haematopoietic cells). GST-SH3 affinity chromatography, baculovirus co-expression, co-immunoprecipitation in haematopoietic cells Current biology : CB High 8805332
2007 WIP (WASP-interacting protein) functions as a chaperone for WASP, protecting it from calpain- and proteasome-mediated degradation; WIP-deficient T cells show severely reduced WASP protein (but not mRNA), and introduction of WIP rescues WASP levels. The WASP-binding domain of WIP is necessary for protection. WIP knockout mouse T cells, proteasome/calpain inhibitor treatment, WASP protein quantification, WIP domain mapping Proceedings of the National Academy of Sciences of the United States of America High 17213309
2008 WASP activity is regulated by two hierarchical mechanisms: (1) allosteric autoinhibition where the VCA domain is sequestered, and (2) dimerization/oligomerization that increases Arp2/3 complex affinity by up to 180-fold, greatly enhancing actin assembly. Dimerization explains activation by bacterial effector EspFu and numerous SH3 domain proteins. In vitro actin assembly assays, biochemical dimerization assays, affinity measurements Molecular cell High 18995840
2005 Cdc42 and the Src family kinase Lck cooperate synergistically to activate WASP: autoinhibition reduces phosphorylation/dephosphorylation efficiency by 30-40-fold, and Cdc42 reverses this; Cdc42 and the SH3-SH2 module of Lck cooperatively stimulate phosphorylated WASP activity with coupling energy of ~2.4 kcal/mol. In vitro kinase assays with purified proteins, actin polymerization assays, quantitative biochemical measurements The Journal of biological chemistry High 16293614
2007 WASp plays an opposing role to PKCtheta in immunological synapse (IS) dynamics: WASp is required for IS reformation after T cell migration, while PKCtheta drives IS symmetry breaking. WASp-deficient T cells display normal initial IS formation but cannot reform the IS after migration unless PKCtheta is inhibited. WASp-/- and PKCtheta-/- T cell imaging, live cell microscopy of IS formation and reformation in vitro and in vivo Cell High 17512410
2007 Differential regulation of WASP and N-WASP by upstream activators: Cdc42 is a more effective activator of WASP than N-WASP; Rac1 exclusively stimulates N-WASP with greater potency than Cdc42; PIP2 vesicles improve N-WASP but not WASP actin nucleation; Nck1/2 are the most potent activators of both with distinct effects. In vitro actin nucleation assays with purified full-length human WASP and N-WASP from mammalian cells, pyrene actin polymerization assays Biochemistry High 17302440
2012 WASP is ubiquitylated following TCR activation; tyrosine phosphorylation of WASP at Y291 recruits E3 ligases Cbl-b and c-Cbl, which ubiquitylate WASP at lysine residues K76 and K81 in the WH1 domain. Disruption of ubiquitylation causes WASP accumulation and altered actin dynamics. TCR stimulation of T cells, ubiquitylation assays, site-directed mutagenesis of K76/K81 and Y291, co-immunoprecipitation of Cbl-b/c-Cbl Molecular and cellular biology High 22665495
2014 Hck (p61 isoform), a leukocyte-predominant Src family kinase, is the primary tyrosine kinase that phosphorylates WASP in macrophages, regulating phagocytosis, chemotaxis, podosome dynamics, matrix degradation, and transendothelial migration. Hck-/- macrophages show severely reduced WASP tyrosine phosphorylation. Hck-/- bone marrow-derived macrophages, Hck siRNA knockdown, functional assays (phagocytosis, chemotaxis, matrix degradation), CX3CL1 and FcγR stimulation The Journal of biological chemistry High 24482227
2014 Tyrosine phosphorylation of WIP triggers release of WASP from the WIP-WASP complex, leading to rapid WASP degradation, podosome disruption, and failure to degrade extracellular matrix. Bruton's tyrosine kinase (Btk) was identified as a regulator of WIP tyrosine phosphorylation. WIP knockdown with phosphomimic expression, WASP stability assays, podosome lifetime measurements, matrix degradation assays, kinase inhibitor screen, Btk identification Journal of cell science High 25413351
2018 Gain-of-function WASp mutations causing X-linked neutropenia (XLN) result in constitutively open WASp conformation due to phosphorylation of tyrosine-293 combined with plasma membrane localization, rendering WASp activity less dependent on PI3K regulation and producing hyperactive neutrophils with increased actin dynamics. XLN patient neutrophils, two XLN mouse models, molecular analysis of WASp conformation, tyrosine phosphorylation analysis, actin dynamics measurements, PI3K inhibition The Journal of clinical investigation High 30124469
2018 WASP and WIP are tumor suppressors in T cell lymphoma; in their absence, active GTP-bound CDC42 is increased, and deletion of one CDC42 allele is sufficient to impair lymphoma growth. ALK-driven STAT3 and C/EBP-β suppress WASP and WIP expression in ALK+ ALCL. WASP/WIP-deficient mice, lymphoma acceleration assays, CDC42-GTP pulldown, CDC42 heterozygous deletion rescue, ALK inhibitor experiments Nature medicine High 30510251
2021 WASP enriches to sites of inward membrane deformation (invaginations) caused by substrate topology, preferentially at their necks, in a front-biased manner set by Cdc42. WASP facilitates Arp2/3 recruitment and local actin assembly at these sites, coupling substrate features to the cytoskeleton; WASP KO cells are defective at topology-directed migration. WASP KO neutrophils, superresolution imaging, live cell imaging on 3D substrates, Arp2/3 localization assays, Cdc42 manipulation The Journal of cell biology High 34964841
2019 WASP contributes to maintenance of front-rear cell polarity by restricting active Rac to the cell front through its CRIB motif; WASP-lacking cells inappropriately activate Rac at the rear. The CRIB motif is required for restricting Rac activity but not for WASP localization to clathrin pits or Arp2/3 activation during endocytosis. Dictyostelium WASP KO, WASP CRIB mutants, FRET-based Rac activity reporters, live cell imaging, endocytosis assays Current biology : CB Medium 31786060
2003 In Drosophila, Abi protein binds WASP through its C-terminal domain and acts as a potent stimulator of WASP-dependent F-actin formation; reduction of abi function causes bristle loss (similar to wasp mutants); this genetic interaction is wasp-specific and not wave-dependent. Drosophila genetics (abi and wasp mutants), biochemical binding assay, F-actin formation assay, epistasis analysis Development (Cambridge, England) Medium 12900458
2005 Abi protein activates WASP-mediated actin polymerization in vivo; Abi binds WASP through its C-terminal domain; abi loss-of-function causes bristle defects rescued by wasp but not wave, establishing Abi as a WASP-specific activator in sensory organ development. Drosophila genetics, biochemical binding, F-actin formation assays, genetic epistasis with wasp and wave mutants Nature cell biology High 16155589
2001 WASP (but not N-WASP) is sensitive to cleavage by calpain (a Ca2+-dependent protease) activated in agonist-stimulated platelets; this differential sensitivity suggests calpain-mediated WASP cleavage functions as a Ca2+-dependent switch terminating the surface projection phase of blood cell activation. Ex vivo broken cell calpain cleavage assays with calpeptin and E64d inhibitors, platelet stimulation experiments Blood Medium 11698281
2013 Aldolase (fructose-1,6-bisphosphate aldolase) binds WASP and sequesters it, inhibiting WASP/Arp2/3-dependent actin polymerization in vitro; this effect depends on aldolase's actin-binding activity (moonlighting function) rather than its catalytic activity. In vitro actin polymerization assays, aldolase knockdown in cells, aldolase catalytic and actin-binding mutants, cell motility/spreading assays Journal of cellular biochemistry Medium 23495010
2007 WIP binds to the N-WASP EVH1 domain through three distinct epitopes (residues 451-461, 461-485, and an extended interface); all three epitopes are required for functional N-WASP binding in cells, with a central polyproline motif occupying the canonical binding site in reversed orientation relative to other EVH1 complexes. NMR structure of WIP-EVH1 complex, site-directed mutagenesis of WIP epitopes, cellular binding assays The Journal of biological chemistry High 17229736
2007 WIP expression is necessary for WASP protein stability and functional expression in human cells; the WIP WASP-binding domain is the minimal region needed to maintain WASP levels, but this minimal domain alone is insufficient to rescue WASP-dependent IL-2 transcriptional activity. WIP knockdown in T cells, WIP domain deletion experiments, WASP protein quantification, NFAT-IL2 reporter assay International immunology Medium 17205972
2016 WASP expression specifically in FOXP3+ Tregs is required to prevent Th2-mediated food allergy; conditional deletion of Was in Tregs results in more severe Th2 intestinal inflammation than global WASP deficiency. WASP-deficient Tregs fail to restrain Th2 effector responses, associated with increased GATA3 expression in effector memory FOXP3+ Tregs. Conditional Was knockout in FOXP3+ Tregs (Cre-loxP), comparison with global WAS KO mice, Th1/Th2/Th17 cytokine profiling, GATA3 expression analysis, germ-free housing experiments The Journal of clinical investigation High 27643438
2007 T cell development requires the combined activity of WASP and N-WASP; double knockout mice show thymic hypocellularity, reduced peripheral T cells, impaired DN-to-DP transition, reduced cycling DN3 cells, and impaired SP cell migration. N-WASP single KO T cells are indistinguishable from WT. RAG2-deficient blastocyst complementation with DKO ES cells; conditional DKO using Cre-loxP; flow cytometry, migration assays Proceedings of the National Academy of Sciences of the United States of America High 17878299
2012 The combined activity of WASP and N-WASP is required for peripheral B cell development (follicular and marginal zone B cells), spreading, migration, antigen uptake, and immune responses to T-independent and T-dependent antigens; single WASP KO B cells show partial defects in migration but not development. Conditional DKO mice (WASP and N-WASP deleted in B cells), flow cytometry, spreading assays, in vivo homing, antigen uptake, antibody response assays Blood High 22411869
2007 Activation of p61Hck triggers WASP- and Arp2/3-dependent actin comet tail formation on lysosomes, accelerating lysosome motility by 35%; this process requires Cdc42 but not Rac or Rho, and was reconstituted in vitro on beads. In vitro actin comet tail reconstitution on p61Hck-positive lysosomes and latex beads in phagocyte cytosol, kinase-dead mutants, WASP-/- cells, Arp2/3 inhibition, GTPase inhibitors The Journal of biological chemistry High 17500055
2016 In C. elegans, WASP functions downstream of MIG-13/SEM-5(Grb2) to activate the Arp2/3 complex during neuroblast migration; purified SEM-5 and MIG-2 synergistically stimulate WASP-Arp2/3 F-actin branching activity in vitro. WASP mutations enhance migration defects in WAVE-deficient cells, indicating partial compensatory roles. C. elegans genetics, GFP knockin, in vitro F-actin branching assay with purified proteins, epistasis analysis with WAVE mutants Developmental cell High 27780040

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nature reviews. Molecular cell biology 753 17183359
1998 Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP. Nature 568 9422512
2015 Endocannabinoid signaling at the periphery: 50 years after THC. Trends in pharmacological sciences 488 25796370
2000 Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP. The Journal of cell biology 363 10662777
2010 WASP: a key immunological multitasker. Nature reviews. Immunology 318 20182458
2007 Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Cell 285 17512410
2003 Clinical course of patients with WASP gene mutations. Blood 275 12969986
2008 Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addiction biology 263 18482430
2010 Physical mechanisms of signal integration by WASP family proteins. Annual review of biochemistry 210 20533885
1999 The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annual review of immunology 177 10358777
2002 Syndapins integrate N-WASP in receptor-mediated endocytosis. The EMBO journal 172 12426380
2008 Hierarchical regulation of WASP/WAVE proteins. Molecular cell 170 18995840
2017 Cellular functions of WASP family proteins at a glance. Journal of cell science 163 28646090
2013 Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling. Cell 158 24267894
2002 WASp in immune-system organization and function. Nature reviews. Immunology 156 12209132
2003 Regulation of actin dynamics by WASP family proteins. Journal of biochemistry 146 14561714
2000 Social wasp (Hymenoptera: Vespidae) foraging behavior. Annual review of entomology 134 10761573
2007 Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology 131 18161012
2007 WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP). Proceedings of the National Academy of Sciences of the United States of America 130 17213309
1996 Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases. Current biology : CB 123 8805332
2009 The WASP and WAVE family proteins. Genome biology 118 19589182
2004 Cortactin regulates cell migration through activation of N-WASP. Journal of cell science 111 15585574
2004 Mechanisms of WASp-mediated hematologic and immunologic disease. Blood 109 15308573
2007 Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Biochemistry 108 17302440
2006 Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Psychopharmacology 103 16572263
2014 Systematic analysis of a wasp parasitism arsenal. Molecular ecology 101 24383716
2020 Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution. Cell 96 33035453
1991 Polydnavirus DNA is integrated in the DNA of its parasitoid wasp host. Proceedings of the National Academy of Sciences of the United States of America 95 1946402
2022 Review of delta-8-tetrahydrocannabinol (Δ8 -THC): Comparative pharmacology with Δ9 -THC. British journal of pharmacology 87 35523678
2007 Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proceedings of the National Academy of Sciences of the United States of America 85 17878299
2011 Mechanisms of immunotherapy to wasp and bee venom. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 79 21729181
1997 Expression of Wiskott-Aldrich syndrome protein (WASP) gene during hematopoietic differentiation. Blood 79 9207440
1997 A polydnavirus-encoded protein of an endoparasitoid wasp is an immune suppressor. The Journal of general virology 78 9367394
2014 The potential therapeutic effects of THC on Alzheimer's disease. Journal of Alzheimer's disease : JAD 77 25024327
2004 The WASP-Arp2/3 pathway: genetic insights. Current opinion in cell biology 77 15196561
2005 Protein-tyrosine kinase and GTPase signals cooperate to phosphorylate and activate Wiskott-Aldrich syndrome protein (WASP)/neuronal WASP. The Journal of biological chemistry 76 16293614
2013 Polydnavirus-wasp associations: evolution, genome organization, and function. Current opinion in virology 75 23816391
2008 Properties of an intergenic terminator and start site switch that regulate IMD2 transcription in yeast. Molecular and cellular biology 75 18426909
2003 Kette regulates actin dynamics and genetically interacts with Wave and Wasp. Development (Cambridge, England) 75 12900458
1999 Signalling to actin: the Cdc42-N-WASP-Arp2/3 connection. Chemistry & biology 70 10467124
2007 WASP-interacting protein (WIP): working in polymerisation and much more. Trends in cell biology 67 17949983
2010 WASP and WAVE family proteins: friends or foes in cancer invasion? Cancer science 66 20707804
2014 Insights into function and evolution of parasitoid wasp venoms. Current opinion in insect science 63 32846678
2018 Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma. Nature medicine 62 30510251
2012 Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function. Blood 61 22411869
2005 Abi activates WASP to promote sensory organ development. Nature cell biology 58 16155589
2000 Simultaneous determination of THC-COOH and THC-COOH-glucuronide in urine samples by LC/MS/MS. Forensic science international 57 10978652
2016 FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy. The Journal of clinical investigation 55 27643438
2009 Recent advances in the biology of WASP and WIP. Immunologic research 53 19018480
1999 Waltzing with WASP. Trends in cell biology 51 10087612
2010 Role of WASP in cell polarity and podosome dynamics of myeloid cells. European journal of cell biology 50 20609498
2012 Ubiquitylation-dependent negative regulation of WASp is essential for actin cytoskeleton dynamics. Molecular and cellular biology 49 22665495
1997 Identification of N-WASP homologs in human and rat brain. Gene 45 9322739
2021 Chromosomal scale assembly of parasitic wasp genome reveals symbiotic virus colonization. Communications biology 44 33483589
2020 Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer. Cancers 43 32340151
2016 Peptide Toxins in Solitary Wasp Venoms. Toxins 43 27096870
2016 Functional Coordination of WAVE and WASP in C. elegans Neuroblast Migration. Developmental cell 43 27780040
2010 THC Prevents MDMA Neurotoxicity in Mice. PloS one 41 20174577
2020 Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin. Scientific reports 40 32994467
1999 WASP levels in platelets and lymphocytes of wiskott-aldrich syndrome patients correlate with cell dysfunction. Journal of immunology (Baltimore, Md. : 1950) 40 10570326
2007 Multiple WASP-interacting protein recognition motifs are required for a functional interaction with N-WASP. The Journal of biological chemistry 39 17229736
2007 Metabolic regulation of IMD2 transcription and an unusual DNA element that generates short transcripts. Molecular and cellular biology 38 17296737
2012 WIP: WASP-interacting proteins at invadopodia and podosomes. European journal of cell biology 37 22823953
2021 WASP integrates substrate topology and cell polarity to guide neutrophil migration. The Journal of cell biology 36 34964841
2015 An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis. Developmental cell 35 26555049
2003 The jewel wasp Nasonia: querying the genome with haplo-diploid genetics. Genesis (New York, N.Y. : 2000) 34 12640624
2018 Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive. The Journal of clinical investigation 33 30124469
2001 WASP and N-WASP in human platelets differ in sensitivity to protease calpain. Blood 33 11698281
2018 Novel behavioral assays of spontaneous and precipitated THC withdrawal in mice. Drug and alcohol dependence 32 30071445
2017 Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information. Progress in neuro-psychopharmacology & biological psychiatry 32 28642081
2013 Aldolase sequesters WASP and affects WASP/Arp2/3-stimulated actin dynamics. Journal of cellular biochemistry 32 23495010
2007 The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP). International immunology 32 17205972
2022 Differential Effects of D9 Tetrahydrocannabinol (THC)- and Cannabidiol (CBD)-Based Cannabinoid Treatments on Macrophage Immune Function In Vitro and on Gastrointestinal Inflammation in a Murine Model. Biomedicines 31 35892693
2011 Interplay between N-WASP and CK2 optimizes clathrin-mediated endocytosis of EGFR. Journal of cell science 30 21610097
2014 N-WASP-directed actin polymerization activates Cas phosphorylation and lamellipodium spreading. Journal of cell science 29 24481817
2005 WASP and the phenotypic range associated with deficiency. Current opinion in allergy and clinical immunology 29 16264326
2020 N-Wasp Regulates Oligodendrocyte Myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 32601246
2014 WIP: more than a WASp-interacting protein. Journal of leukocyte biology 28 25210148
2019 Quantifying Hepatic Enzyme Kinetics of (-)-∆9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, 11-OH-THC, through In Vitro Modeling. Drug metabolism and disposition: the biological fate of chemicals 27 31048453
2022 Bioactive Peptides and Proteins from Wasp Venoms. Biomolecules 26 35454116
2018 Hepatic Enzymes Relevant to the Disposition of (-)-∆9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, 11-OH-THC. Drug metabolism and disposition: the biological fate of chemicals 26 30567877
2016 WASP family proteins, more than Arp2/3 activators. Biochemical Society transactions 26 27911716
2016 Short-term exposure and long-term consequences of neonatal exposure to Δ(9)-tetrahydrocannabinol (THC) and ibuprofen in mice. Behavioural brain research 25 27058925
2015 Deletion of WASp and N-WASp in B cells cripples the germinal center response and results in production of IgM autoantibodies. Journal of autoimmunity 25 26143192
2019 FABP1 controls hepatic transport and biotransformation of Δ9-THC. Scientific reports 24 31110286
2014 Tyrosine phosphorylation of Wiskott-Aldrich syndrome protein (WASP) by Hck regulates macrophage function. The Journal of biological chemistry 23 24482227
2012 Combined effects of THC and caffeine on working memory in rats. British journal of pharmacology 23 21699509
2010 Regulation of WASp by phosphorylation: Activation or other functions? Communicative & integrative biology 23 20585499
2024 An emerging trend in Novel Psychoactive Substances (NPSs): designer THC. Journal of cannabis research 22 38702834
2022 Juvenile hormone as a causal factor for maternal regulation of diapause in a wasp. Insect biochemistry and molecular biology 20 35276333
2004 FBP11 regulates nuclear localization of N-WASP and inhibits N-WASP-dependent microspike formation. Biochemical and biophysical research communications 20 14697212
2023 Selected cannabis terpenes synergize with THC to produce increased CB1 receptor activation. Biochemical pharmacology 19 37084981
2020 Early Exposure to THC Alters M-Cell Development in Zebrafish Embryos. Biomedicines 19 31947970
2020 Wasp venom peptide as a new antichagasic agent. Toxicon : official journal of the International Society on Toxinology 19 32360153
2019 WASP Restricts Active Rac to Maintain Cells' Front-Rear Polarization. Current biology : CB 19 31786060
2008 Transcriptional repression of the IMD2 gene mediated by the transcriptional co-activator Sub1. Genes to cells : devoted to molecular & cellular mechanisms 19 18823333
2020 THC Regulates Tearing via Cannabinoid CB1 Receptors. Investigative ophthalmology & visual science 18 32852544
2014 Tyrosine phosphorylation of WIP releases bound WASP and impairs podosome assembly in macrophages. Journal of cell science 18 25413351
2007 Activation of p61Hck triggers WASp- and Arp2/3-dependent actin-comet tail biogenesis and accelerates lysosomes. The Journal of biological chemistry 18 17500055
2003 The critical cis-acting element required for IMD2 feedback regulation by GDP is a TATA box located 202 nucleotides upstream of the transcription start site. Molecular and cellular biology 18 12917347

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