Affinage

NCK1

SH2/SH3 adapter protein NCK1 · UniProt P16333

Length
377 aa
Mass
42.9 kDa
Annotated
2026-04-29
100 papers in source corpus 50 papers cited in narrative 51 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NCK1 is an SH2/SH3-domain adaptor protein that couples tyrosine-phosphorylated receptors and scaffolds to actin cytoskeletal remodeling, signal transduction, and nuclear checkpoint signaling across diverse cellular contexts. Its single SH2 domain recognizes phosphotyrosine-containing motifs (notably pYDXV) on substrates including nephrin, EPEC Tir, p130Cas, cortactin, IRS-1, SLP-76, and CEACAM3, while its three SH3 domains recruit proline-rich effectors—N-WASP/WASP (directly and via WIP), PAK1, Sos, dynamin, Vav1, and capping enzyme—to drive Arp2/3-dependent actin nucleation, with a critical inter-SH3 linker that allosterically activates N-WASP and promotes phase separation of signaling assemblies (PMID:11340081, PMID:26554011, PMID:26553976, PMID:12181570). NCK1 functions in receptor tyrosine kinase signaling (PDGFR via p130Cas, VEGFR, EphB1), immune synapse organization (TCR–CD3ε, BCR–Igα, SLP-76–Vav1), endothelial polarity and angiogenesis (ROBO1–Cdc42–Pak2), pathogen exploitation (EPEC pedestals, vaccinia actin tails, picornavirus entry), and invadopodia-driven tumor invasion (PMID:16769879, PMID:26659946, PMID:11533668, PMID:12007418, PMID:31769754, PMID:20971703). Beyond cytoplasmic actin signaling, SOCS7-mediated nuclear import of NCK1 enables ATM/ATR-dependent p53 Ser15 phosphorylation for DNA-damage checkpoint activation, and NCK1 is selectively regulated by c-Cbl ubiquitination at K178 (antagonized by synaptopodin) and c-ABL phosphorylation at Y105 (PMID:17803907, PMID:24287595, PMID:22327338).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1992 High

    Identification of NCK1 as a transforming SH2/SH3 adaptor that binds phosphotyrosine proteins and serine/threonine kinases established its potential as a signaling hub coupling receptor activation to downstream effectors.

    Evidence Overexpression transformation assay (soft agar, nude mice) and GST pulldown from mammalian fibroblasts

    PMID:1280326

    Open questions at the time
    • No specific receptor or effector identified
    • Transformation mechanism not resolved
  2. 1995 High

    Mapping of SH3 domain-specific interactions with WASP and NAK/PAK established that NCK1 uses distinct SH3 domains to recruit defined effector kinases and actin regulators, answering how domain architecture encodes effector specificity.

    Evidence GST pulldown and co-immunoprecipitation with domain mapping for WASP (third SH3) and NAK (second SH3)

    PMID:7565724 PMID:7706279

    Open questions at the time
    • Functional consequence of WASP binding on actin not yet tested
    • Catalytic role of NAK undefined
  3. 1996 High

    Demonstration that PAK1 constitutively associates with NCK via the second SH3 domain and that PAK1 phosphorylates NCK revealed a bidirectional kinase–adaptor relationship central to Rho-family GTPase signaling.

    Evidence Co-immunoprecipitation in COS-7/Swiss 3T3 cells, domain mutagenesis, in vitro kinase assay

    PMID:8824201

    Open questions at the time
    • In vivo significance of PAK1-mediated NCK phosphorylation unclear
    • Downstream targets not identified
  4. 1997 High

    Identification of NCK SH2 binding to phospho-p130Cas downstream of FAK/fibronectin and to IRS-1 after insulin stimulation defined the receptor-proximal inputs that recruit NCK to integrin and insulin signaling complexes.

    Evidence In vitro FAK phosphorylation of p130Cas, co-immunoprecipitation, ERK2 readout; SH2 binding assay with IRS-1 phosphopeptides

    PMID:8265614 PMID:9032297

    Open questions at the time
    • Relative contribution of p130Cas vs direct receptor binding not quantified
    • Actin phenotype downstream of IRS-1–NCK not assessed
  5. 1998 High

    Discovery of NCK recruitment to EphB1 at pY594 and the NCK–PAK1 module downstream of TCR for NFAT activation extended the adaptor's role beyond growth factor receptors into axon guidance and T cell activation.

    Evidence Yeast two-hybrid, mutagenesis (Y594F), JNK/NFAT reporter assays, dominant-negative NCK/PAK in T cells

    PMID:9430661 PMID:9755165

    Open questions at the time
    • Whether NCK1 or NCK2 is the relevant paralog in each context not distinguished
    • Structural basis for EphB1-NCK interaction unknown
  6. 2001 High

    In vitro reconstitution showing that NCK SH3 domains directly and allosterically activate N-WASP to stimulate Arp2/3-dependent actin nucleation, together with genetic proof that NCK is essential for EPEC Tir-induced actin pedestals, established the core NCK→N-WASP→Arp2/3 actin nucleation pathway.

    Evidence Purified-protein actin nucleation assay with SH3 domain mutants; Nck1/2 double-knockout MEFs resistant to EPEC pedestal formation

    PMID:11340081 PMID:11533668

    Open questions at the time
    • Mechanism of N-WASP autoinhibition relief by NCK not yet resolved at atomic level
    • Stoichiometry of activation not determined
  7. 2002 High

    Dissection of the WAVE complex showed that NCK (and Rac1) activate actin polymerization by dissociating the inhibitory WAVE1–PIR121–Nap125–HSPC300 complex, while vaccinia studies revealed a hierarchical Nck→WIP/N-WASP→Grb2 assembly pathway for pathogen actin motility.

    Evidence Biochemical reconstitution of native WAVE complex, in vitro actin nucleation; dominant-negative/knockout cells with phosphomutant vaccinia A36R

    PMID:12007418 PMID:12181570

    Open questions at the time
    • Whether NCK acts on WAVE via direct binding or indirectly through Rac1 not fully resolved
    • WAVE complex dissociation model later revised
  8. 2006 High

    Crystal structures of NCK1/NCK2 SH2 domains bound to Tir pYDXV peptides defined the structural basis for phosphotyrosine recognition, while nephrin–Fyn–NCK and Tks5–NCK studies at invadopodia generalized the pYDXV/phosphotyrosine recruitment mechanism across physiological and pathological contexts.

    Evidence X-ray crystallography with fluorescence polarization; co-immunoprecipitation and Fyn kinase assays for nephrin; direct binding and siRNA with matrix degradation assay for Tks5

    PMID:16543952 PMID:16636066 PMID:19596797

    Open questions at the time
    • How NCK1 vs NCK2 selectivity is achieved given nearly identical SH2 structures remains unclear
    • GIT1 interaction not functionally characterized
  9. 2006 High

    Demonstration that NCK binds CD3ε PRS via SH3.1 and p130Cas (not PDGFβR directly) in PDGF signaling refined the proximal binding partners in immune and growth factor pathways, and Nck-null MEFs showed abolished chemotaxis and membrane ruffling.

    Evidence CD3ε PRS knockin mouse with T cell assays; Nck-knockout MEFs with phosphoproteomics and chemotaxis

    PMID:16769879 PMID:24470497

    Open questions at the time
    • Whether CD3ε-NCK interaction precedes or follows Lck-dependent ITAM phosphorylation debated
    • p130Cas phosphosite(s) for NCK not mapped
  10. 2007 High

    The discovery that SOCS7 carries NCK into the nucleus upon septin depletion, where it enables ATM/ATR-dependent p53 Ser15 phosphorylation, revealed an unexpected nuclear checkpoint function for a canonical cytoplasmic adaptor.

    Evidence siRNA knockdown of septins/SOCS7, nuclear/cytoplasmic fractionation, rescue with cytoplasmic vs nuclear NCK constructs, cell-cycle analysis

    PMID:17803907

    Open questions at the time
    • Nuclear binding partners and direct substrate of NCK in the nucleus unknown
    • Whether this applies to NCK2 not tested
  11. 2010 High

    Identification of NCK1 as a phosphotyrosine-dependent recruiter to cortactin at invadopodia (pY421/466) and as a modulator of hepatic ER stress (IRE1α/JNK axis) extended NCK1 function to tumor invasion and metabolic regulation.

    Evidence FRET, mutagenesis, invasion assay for cortactin; Nck1 KO mice with glucose tolerance and ER stress markers

    PMID:20587749 PMID:20971703

    Open questions at the time
    • Direct binding of NCK1 to IRE1α not shown
    • Whether invadopodial NCK1 function is redundant with NCK2 not tested
  12. 2012 High

    Quantitative stoichiometry (4 Nck:2 N-WASP:1 Arp2/3), the SLP-76–Nck–Vav1 trimolecular FRET complex at the immune synapse, and c-ABL-mediated Y105 phosphorylation provided mechanistic refinement of how NCK density, partner cooperativity, and post-translational modification tune signaling output.

    Evidence Quantitative fluorescence microscopy with computational modeling; triple-color FRET in live T cells; in vitro kinase assay with NCK1 Y105 mutants

    PMID:22327338 PMID:22534133 PMID:22613834

    Open questions at the time
    • How NCK density threshold is set in vivo remains unclear
    • Physiological contexts where Y105 phosphorylation is rate-limiting not defined
  13. 2013 High

    Paralog-selective regulation was established: c-Cbl ubiquitinates NCK1 (not NCK2) at K178 to control its stability and RhoA/actin stress fibers, while NCK binds Igα pY204 to recruit BCAP for PI3K–Akt signaling in B cells, and WIP bridges NCK SH3.2 to N-WASP during vaccinia motility.

    Evidence Ubiquitination assay with K178R mutant, siRNA, co-IP; conditional Nck KO mice with B cell assays; Nck/WIP/N-WASP null MEFs with live imaging

    PMID:23707428 PMID:23913047 PMID:24287595

    Open questions at the time
    • Synaptopodin–c-Cbl competition not structurally resolved
    • Whether BCAP recruitment is NCK1- or NCK2-specific unknown
  14. 2014 High

    NCK1 was identified as the scaffold for the cytoplasmic mRNA capping complex (capping enzyme + 5′ kinase on SH3.1/SH3.3), and as the selective activator of IRAK-1–NF-κB in endothelial cells under disturbed flow (via SH2 and SH3.1), establishing new non-actin functions.

    Evidence In vitro reconstitution of capping complex on recombinant NCK1, knockdown and SH3 mutagenesis; domain-swap experiments, NCK1–IRAK-1 co-IP, Nck1 KO mice with NF-κB readout

    PMID:25137142 PMID:32427580

    Open questions at the time
    • How capping complex activity is regulated by receptor signals unknown
    • IRAK-1 activation mechanism by NCK1 not biochemically defined
  15. 2015 High

    Biophysical studies revealed that the NCK inter-SH3 linker allosterically relieves N-WASP autoinhibition by engaging the GBD and promotes phase separation of Nck/N-WASP/nephrin signaling clusters, providing a molecular mechanism for signal amplification at membranes.

    Evidence Purified-protein phase separation assays with linker mutants; in vitro actin assembly reconstitution with GBD-binding analysis

    PMID:26553976 PMID:26554011

    Open questions at the time
    • Phase separation not yet confirmed in intact podocytes in vivo
    • Contribution of each linear motif in the linker not fully quantified
  16. 2015 High

    Endothelial-specific Nck1/2 deletion in mice demonstrated that NCK is required for ROBO1-mediated Cdc42/Pak2 activation, front-rear polarity, and sprouting angiogenesis, establishing an essential in vivo vascular function.

    Evidence Inducible endothelial Nck1/2 conditional KO mice, retinal angiogenesis imaging, Cdc42/Pak2 activation assays

    PMID:26659946

    Open questions at the time
    • Whether NCK1 and NCK2 are individually sufficient for angiogenesis not resolved
    • Downstream effectors linking Pak2 to polarity not identified
  17. 2018 High

    Proteomic mapping of NCK1- vs NCK2-specific interactomes (30 NCK1-specific, 28 NCK2-specific partners) revealed that NCK2 selectively controls cytokinesis abscission while NCK1 does not, sharpening the functional distinction between paralogs.

    Evidence AP-MS and BioID in Nck1−/− and Nck2−/− MEFs, time-lapse microscopy of cytokinesis defects

    PMID:30002203

    Open questions at the time
    • NCK1-specific interactors not functionally validated
    • Structural basis for paralog selectivity unknown
  18. 2019 High

    CRISPR genetic epistasis placed NCK1 in a TNK2→NCK1→N-WASP pathway required for picornavirus entry, demonstrating that pathogen exploitation of the NCK1-actin axis extends beyond bacteria to RNA viruses.

    Evidence CRISPR triple-KO epistasis, viral internalization assays for EMCV/CVB3/poliovirus/EV-D68

    PMID:31769754

    Open questions at the time
    • Whether TNK2 directly phosphorylates NCK1 or an upstream scaffold not determined
    • Host receptor providing the tyrosine-phosphorylated docking site for NCK1 not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how NCK1 vs NCK2 paralog selectivity is structurally encoded despite near-identical SH2 domains; (2) the in vivo relevance and regulation of NCK1-driven phase separation at signaling membranes; (3) the direct nuclear substrates or partners mediating NCK1's checkpoint function; and (4) whether the capping-complex scaffold and IRAK-1 activation roles are coordinated with or independent of actin remodeling.
  • Structural basis for NCK1/NCK2 selectivity
  • In vivo phase separation confirmation
  • Nuclear NCK1 interaction partners
  • Mechanistic link between capping complex and actin functions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 10 GO:0008092 cytoskeletal protein binding 5
Localization
GO:0005886 plasma membrane 7 GO:0005829 cytosol 4 GO:0005856 cytoskeleton 4 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 12 R-HSA-168256 Immune System 7 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2 R-HSA-73894 DNA Repair 2
Partners
NPHS1PAK1ROBO1SLP76SOCS7WASWASLWIPF1
Complex memberships
Cytoplasmic capping complex (CE/5′ kinase/Nck1)Nck/N-WASP/Arp2/3 actin nucleation complexSLP-76/Nck/Vav1 trimolecular complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 WAVE1 exists in an inactive heterotetrameric complex with PIR121, Nap125, and HSPC300; Rac1 and Nck cause dissociation of this complex, releasing active WAVE1-HSPC300 and leading to actin nucleation through the Arp2/3 pathway. Biochemical reconstitution, purification of native complex, in vitro actin nucleation assay Nature High 12181570
2001 Nck SH3 domains directly and dramatically stimulate actin nucleation by purified N-WASP in the presence of Arp2/3 in vitro; all three SH3 domains are required for maximal activation, and Nck and Cdc42 activate N-WASP by redundant mechanisms. In vitro actin nucleation assay with purified recombinant proteins, domain mutagenesis The Journal of biological chemistry High 11340081
2001 EPEC Tir is phosphorylated on tyrosine 474, which directly binds Nck; Nck is required for recruitment of N-WASP and Arp2/3 to EPEC pedestals, directly linking Tir to actin cytoskeleton remodeling. Cells null for both Nck genes are resistant to EPEC-induced actin pedestal formation. Genetic null cells (Nck1/2 double knockout), co-immunoprecipitation, direct binding assay Nature cell biology High 11533668
1995 Nck SH3 domains, particularly the C-terminal (third) SH3 domain, physically associate with WASP (Wiskott-Aldrich syndrome protein) in vivo and in vitro. In vivo and in vitro binding assays (GST pulldown, co-immunoprecipitation), domain mapping Molecular and cellular biology High 7565724
1996 Nck binds PAK1 through its second SH3 domain; PAK1 interacts with Nck via the first proline-rich SH3-binding motif at its amino terminus. Association is constitutive but strengthened by PDGF receptor stimulation, and active PAK1 phosphorylates Nck at multiple sites. Co-immunoprecipitation in COS-7 and Swiss 3T3 cells, GST pulldown, domain mutagenesis, in vitro kinase assay The Journal of biological chemistry High 8824201
1993 Nck SH2 domain binds tyrosine-phosphorylated IRS-1 in insulin-stimulated cells; Nck, Grb2, and p85 bind distinct phosphotyrosine residues on a single IRS-1 molecule. Co-immunoprecipitation in insulin-stimulated cells, in vitro SH2 binding assay with phosphopeptides Proceedings of the National Academy of Sciences of the United States of America High 8265614
2007 Septin knockdown causes nuclear accumulation of NCK via SOCS7, which carries NCK into the nucleus through its nuclear import/export signals; nuclear NCK is responsible for actin stress fiber disintegration and cell cycle arrest. NCK is essential for p53 Ser15 phosphorylation downstream of ATM/ATR. siRNA knockdown, live-cell imaging, nuclear/cytoplasmic fractionation, rescue experiments with cytoplasmic vs nuclear NCK, co-immunoprecipitation Cell High 17803907
2006 Nephrin ectodomain engagement induces Fyn kinase activity, which phosphorylates specific nephrin cytoplasmic tyrosine residues; phosphorylated nephrin recruits Nck (via its SH2 domain), and Nck-dependent actin filament assembly follows. Biochemical signaling assays, co-immunoprecipitation, dominant-negative/knockdown experiments The Journal of clinical investigation High 16543952
2010 Cortactin tyrosines 421 and 466 (but not 482) are phosphorylated and required for Nck1 recruitment to invadopodia via its SH2 domain; Nck1 binding to phospho-cortactin is direct (in vitro pulldown) and FRET-confirmed in cells; this drives actin barbed-end generation and tumor cell invasion. In vitro direct binding assay, FRET in cells, site-directed mutagenesis, knockdown with invasion assay Journal of cell science High 20971703
2003 Akt phosphorylates PAK1 at serine 21, which reduces Nck binding to PAK1; Nck normally binds PAK1 near serine 21, and disruption of this interaction (by Akt or a competing Tat-Nck peptide) releases PAK1 from focal adhesions and reduces Akt-stimulated cell migration. In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, cell migration assay, GFP-tagged protein imaging Molecular and cellular biology High 14585966
2008 Multiple phosphorylated YDXV motifs on nephrin recruit Nck via its SH2 domain cooperatively; multiple Nck SH3 domains act cooperatively to induce actin polymerization. YDXV/Nck signaling is a portable mechanism also used by EPEC Tir (molecular mimicry). Mutagenesis of nephrin pYDXV motifs and Nck SH3 domains, actin polymerization assay, co-immunoprecipitation Molecular and cellular biology High 18212058
2015 A 50-residue linker between the first two SH3 domains of Nck promotes phase separation of Nck/N-WASP/nephrin assemblies through weak interactions with the second SH3 domain and positive charge; two linear motifs within the linker are critical for this effect. Phase separation assay with purified proteins, linker mutagenesis, biophysical characterization Proceedings of the National Academy of Sciences of the United States of America High 26553976
2015 An inter-SH3 linker sequence within Nck (between SH3-1 and SH3-2) allosterically activates N-WASP by directly engaging the N-WASP GBD and competing with VCA binding, relieving autoinhibition to promote actin assembly. In vitro reconstitution of actin assembly with purified proteins, direct binding assay, mutagenesis of linker motifs Proceedings of the National Academy of Sciences of the United States of America High 26554011
2013 WIP is recruited to vaccinia virus by binding the second SH3 domain of Nck; WIP bound to N-WASP acts as an essential link between Nck and N-WASP. The first and third SH3 domains of Nck are not needed for WIP:N-WASP recruitment but are essential to stimulate Arp2/3-dependent actin assembly. MEFs lacking Nck, WIP, or N-WASP; domain mutagenesis; live-cell imaging of vaccinia actin motility Current biology : CB High 23707428
2006 Crystal structures of Nck1 and Nck2 SH2 domains in complex with EPEC Tir phosphopeptides show highly conserved, specific recognition of the pYDXV phosphopeptide motif; binding specificities of Nck1 and Nck2 SH2 domains are essentially indistinguishable. GIT1 was confirmed as a new Nck binding partner. X-ray crystallography, fluorescence polarization binding assays, phosphopeptide array The Journal of biological chemistry High 16636066
2013 Nck1, but not Nck2, is ubiquitinated by c-Cbl at lysine 178, leading to proteasomal degradation; synaptopodin competes with c-Cbl for Nck1 binding, preventing this ubiquitination. Nck1 degradation modulates RhoA activation and actin stress fiber formation. Ubiquitination assay, site-directed mutagenesis (K178R), siRNA, co-immunoprecipitation, actin imaging Nature communications High 24287595
2013 Nck binds directly to BCR component immunoglobulin-α at the non-ITAM phosphotyrosine at position 204; Nck recruits BCAP to sites of BCR signaling to modulate the PI(3)K-Akt pathway in B cells. Genetic ablation of Nck impairs BCR signaling, B cell survival, proliferation, and antibody responses. Direct binding assay, co-immunoprecipitation, conditional Nck knockout mice, B cell functional assays Nature immunology High 23913047
1998 Nck is recruited to EphB1 (ELK) at the juxtamembrane Tyr594 upon ligand activation; Nck recruitment is required for JNK activation and cell attachment responses downstream of EphB1. Yeast two-hybrid cloning, co-immunoprecipitation, site-directed mutagenesis (Y594F), dominant-negative overexpression, JNK kinase assay The Journal of biological chemistry High 9430661
1998 A Nck-Pak1 signaling module is required downstream of TCR activation for NFAT and Erk2 activation, but not JNK; TCR stimulation induces Nck tyrosine phosphorylation and Pak1 association with Nck; dominant-negative Nck or Pak1 specifically block NFAT activation. Co-immunoprecipitation, dominant-negative overexpression, kinase activity assay, reporter gene assay The EMBO journal High 9755165
1992 Overexpression of human Nck (SH2-SH3 adaptor) transforms mammalian fibroblasts; Nck binds tyrosine-phosphorylated proteins and serine/threonine kinases through its SH2 and SH3 domains. Transformation assay (soft agar, nude mice), GST-Nck pulldown, phosphotyrosine binding assay Molecular and cellular biology High 1280326
2002 Nck1 SH3 domains (not SH2) interact directly with DCC receptor constitutively in neurons; dominant-negative Nck1 inhibits DCC-induced neurite outgrowth and Rac1 activation in response to netrin-1. Co-immunoprecipitation, direct binding assay with isolated domains, dominant-negative expression, Rac1 GTP-loading assay The Journal of biological chemistry Medium 12149262
1997 FAK-induced phosphorylation of p130cas promotes SH2 domain-dependent binding of Nck to p130cas in fibronectin-stimulated cells, facilitating signaling to ERK2. In vitro phosphorylation assay (FAK phosphorylates p130cas), co-immunoprecipitation with Src domain mutants, ERK2 activity assay Molecular and cellular biology High 9032297
1997 A casein kinase I isoform (CKI-γ2) constitutively associates with Nck through its third SH3 domain in vivo; CKI-γ2 kinase activity co-immunoprecipitates with Nck in insulin receptor-overexpressing hepatocytes. Yeast two-hybrid, co-immunoprecipitation, in vitro renaturation kinase assay, far-western analysis The Journal of biological chemistry Medium 9006905
2002 Nck's first and third SH3 domains interact with the β-subunit of eIF2 (eIF2β); Nck is present in ribosomal fractions and its association is enhanced by insulin; overexpression of Nck-1 enhances cap-dependent and cap-independent protein translation in cells and in vitro, requiring intact first and third SH3 domains. Co-immunoprecipitation, cell fractionation, in vitro translation assay, SH3 domain mutagenesis Proceedings of the National Academy of Sciences of the United States of America Medium 11959995
1999 Nck SH2 domain mediates binding to tyrosine-phosphorylated SLP-76 at Y113 and Y128 in activated T cells; Nck also associates with Cbl (120 kDa) in T cell immunoprecipitates. Co-immunoprecipitation, in vitro SH2 binding assay with competing phosphopeptides European journal of immunology Medium 10229072
2003 Nckβ SH2 domain binds Disabled 1 (Dab1) phosphorylated at Y220 (Reelin-regulated site) or Y232; Nckβ colocalizes with Dab1 in neurons, redistributes into neuronal processes upon Reelin stimulation, and cooperates with tyrosine-phosphorylated Dab1 to disrupt the actin cytoskeleton. Co-immunoprecipitation, SH2 binding assay, live-cell imaging in neurons, Drosophila genetic enhancement assay Molecular and cellular biology Medium 14517291
2006 Src phosphorylates Tks5 at Y557; phospho-Tks5 directly associates with Nck1 and Nck2 SH2 domains at invadopodia. Tks5 mutants unable to bind Nck show reduced matrix degradation and actin recruitment; Nck1 depletion inhibits Src/Tks5-driven matrix proteolysis. In vitro direct binding assay, co-immunoprecipitation, siRNA knockdown, matrix degradation assay, live-cell imaging Journal of cell science High 19596797
2012 Nck/N-WASp/Arp2/3 stoichiometry for actin polymerization is 4:2:1; the density of Nck molecules in membrane aggregates is the critical determinant of actin polymerization, as shown by quantitative live-cell microscopy and computational modeling. Antibody-induced membrane aggregation of Nck SH3 domains, quantitative fluorescence microscopy, computational modeling (Virtual Cell) The Journal of cell biology High 22613834
2009 Nck is essential for actin remodeling stimulated by PI(4,5)P2; PI(4,5)P2 is reciprocally required for localized actin polymerization induced by Nck; PIP5K activity creates tyrosine-phosphorylated Nck SH2 binding partners, suggesting Nck couples phosphotyrosine and phosphoinositide signals. Nck knockdown/knockout, PIP5K overexpression, co-clustering experiments with inositol 5-phosphatase, actin comet assay Molecular cell High 19917259
2012 Nck directly modulates nephrin tyrosine phosphorylation by forming a signaling complex with Fyn kinase via its SH3 domains; Nck SH3 domain mutations or Src kinase inhibition abrogate Nck's ability to enhance nephrin phosphorylation. In vivo loss of Nck in podocytes rapidly reduces nephrin phosphorylation. Co-immunoprecipitation, SH3 domain mutagenesis, pharmacological inhibition, conditional Nck knockout in podocytes The Journal of biological chemistry High 23188823
2014 Nck1 SH3 domains 1 and 3 bind the proline-rich C-terminus of mammalian capping enzyme (CE); Nck1 serves as the scaffold for assembly of the cytoplasmic capping complex (CE + 5' kinase juxtaposed on adjacent Nck1 domains). Nck1 knockdown disrupts capping complex integrity; mutations inactivating each Nck1 SH3 domain inhibit cap homeostasis. Co-immunoprecipitation, in vitro reconstitution on recombinant Nck1, gel filtration/sedimentation, Nck1 knockdown, SH3 domain mutagenesis PLoS biology High 25137142
2015 NCK1 and NCK2 are required for endothelial cell front-rear polarity and sprouting angiogenesis; NCK binding to ROBO1 is required for both Slit2- and VEGF-induced Cdc42 and Pak2 activation and front-rear polarity. Endothelial-specific Nck1/2 deletion in mice causes severe angiogenesis defects. Inducible endothelial-specific Nck1/2 conditional knockout mice, co-immunoprecipitation (NCK-ROBO1), Cdc42/Pak2 activation assays, retinal angiogenesis imaging Circulation High 26659946
2014 NCK1 SH2 domain and first SH3 domain are critical for disturbed flow-induced NF-κB activation; NCK1 selectively binds IRAK-1 (not NCK2), and IRAK-1 activation by disturbed flow requires NCK1 in vitro and in vivo. NCK1 couples PECAM-1 tyrosine phosphorylation to PAK-mediated NF-κB activation. Domain-swap/point mutation experiments, co-immunoprecipitation (NCK1-IRAK-1), siRNA, Nck1-knockout mice, NF-κB reporter assay The Journal of clinical investigation High 32427580
2018 Proteomic analysis identifies NCK1- and NCK2-specific interaction networks (98 proteins, 30 NCK1-specific, 28 NCK2-specific); NCK2, but not NCK1, is required for cytokinesis abscission—NCK2 loss causes multinucleation, extended intercellular bridges, and mislocalization of AURKB, PLK1, and ECT2 at the midbody. NCK2 function in cytokinesis requires its SH2 domain. Affinity purification-mass spectrometry, BioID proximity labeling, Nck1-/- and Nck2-/- MEFs, time-lapse microscopy, immunofluorescence Molecular & cellular proteomics : MCP High 30002203
2002 Grb2 cooperates with Nck for actin-based vaccinia virus motility; Nck recruits N-WASP (via WIP) and is required for initial assembly of the actin-nucleating complex on vaccinia; Grb2 is recruited subsequently through the N-WASP polyproline region and stabilizes/activates the complex. Nck binds A36R pTyr112; Grb2 binds A36R pTyr132. Dominant-negative and knockout cell experiments, phosphomutant virus (A36R Y112F, Y132F), live-cell imaging of actin tails Current biology : CB High 12007418
2006 Nck is recruited to the TCR complex through its SH3.1 domain binding to the proline-rich sequence (PRS) in CD3ε; disruption of this interaction (PRS knockin mutation or blocking peptide) impairs very early TCR signaling including CD3ζ phosphorylation and prevents efficient T cell activation in vitro and in vivo. Knockin mouse (KI-PRS), inhibitory peptide, T cell activation assays, phosphorylation analysis, autoimmune disease model Journal of immunology (Baltimore, Md. : 1950) High 24470497
2012 SLP-76, Nck, and Vav1 form a trimolecular signaling complex at the T cell-APC interface; Nck and Vav1 are constitutively dimerized independently of T cell activation, and TCR stimulation-induced SLP-76 phosphorylation enables Nck binding. The Nck-Vav1 dimer (via Nck SH3-Vav1 proline-rich interaction) is critical for actin rearrangement. Triple-color FRET in live T cells, point mutation of Vav1 proline-rich site, actin rearrangement assay Science signaling High 22534133
2011 Nck is necessary but insufficient for WASp recruitment downstream of TCR; SLP-76 acid domain enables Nck SH2 binding, while SLP-76 SH2 domain enables ADAP interaction. Functional cooperation between Nck and ADAP is required for SLP-76-WASp complex formation and actin rearrangement. Knockdown (siRNA), domain mutants, co-immunoprecipitation, actin imaging Molecular and cellular biology Medium 21536650
2012 Nck1 and Nck2 SH2 domains bind phosphorylated CEACAM3 ITAM-like sequence and localize the WAVE complex to CEACAM3, promoting lamellipodial actin assembly and bacterial phagocytosis. Nck knockdown or SH2 domain overexpression blocks internalization. Co-immunoprecipitation (phosphorylation-dependent), RNAi knockdown, genetic deletion of Nck1/Nck2, bacterial internalization assay PloS one Medium 22448228
2013 Cdc42, activated by the Rho-GEF intersectin-1 (ITSN1) recruited to vaccinia virus, cooperates with Nck to stabilize N-WASP beneath the virus and promote actin tail formation; ITSN1-Cdc42-N-WASP form a feed-forward loop, and this mechanism also operates during FcγR-mediated phagocytosis. Depletion/knockout of ITSN1, Cdc42, and N-WASP; live-cell imaging of vaccinia actin tails; phagocytosis assay Journal of cell science Medium 24284073
2001 Nck associates with the adaptor complex Fyb/SLAP, SLP-76, VASP, and WASP during FcγR-mediated phagocytosis in macrophages; Nck promotes WASP recruitment to the phagocytic cup for actin polymerization and pseudopodium extension. Co-immunoprecipitation (native complex), immunofluorescence colocalization during phagocytosis Journal of cell science Medium 11739662
1995 Nck SH3 domains (second domain primary) bind a serine/threonine kinase (NAK/Nck-associated kinase) in vivo and in vitro. GST pulldown, in vitro binding with isolated SH3 domains, co-immunoprecipitation from multiple cell types The Journal of biological chemistry Medium 7706279
2001 NCK and PAK are constitutively associated in the absence of VEGF; VEGF stimulation augments PAK kinase activity and recruits PAK to focal adhesions; antisense knockdown of NCK inhibits VEGF-induced focal adhesion assembly and endothelial cell migration. Co-immunoprecipitation, antisense oligonucleotide knockdown, migration assay, PAK kinase activity assay The Journal of biological chemistry Medium 11278553
2006 Nck binding to p130Cas (not PDGFβR itself) is the major SH2-dependent interaction in PDGF-B-stimulated cells; Nck-deficient cells fail to form membrane ruffles or disassemble actin bundles in response to PDGF-B, and Nck-null cells lack chemotaxis toward PDGF-B. Nck knockout MEFs, phosphoproteomic analysis, co-immunoprecipitation, actin imaging, chemotaxis assay Proceedings of the National Academy of Sciences of the United States of America High 16769879
2006 Nck FasL interaction: Nck binds to the proline-rich portion of FasL via its SH3 domains and alters FasL subcellular distribution; in cytotoxic T lymphocytes, TCR engagement drives actin-dependent transport of Nck-associated FasL-bearing secretory lysosomes to the immunological synapse. Co-immunoprecipitation, cotransfection redistribution assay, immunofluorescence in T cell-target cell conjugates Proceedings of the National Academy of Sciences of the United States of America Medium 16595635
2010 Nck1 deletion in obese mice attenuates IRE1α and JNK activation, reduces IRS-1 Ser307 phosphorylation, and improves insulin signaling and glucose disposal in liver; Nck1 siRNA in HepG2 cells decreases thapsigargin-induced IRE1α activation. Nck1 modulates the hepatic unfolded protein response. Nck1 knockout mice (obese model), siRNA in hepatocytes, glucose tolerance test, insulin signaling assays, ER stress markers American journal of physiology. Endocrinology and metabolism Medium 20587749
1999 The third (C-terminal) SH3 domain of Nck exclusively binds Sos; the same third SH3 domain also binds dynamin (identified as a 100-kDa Nck-associated protein), linking Nck to Ras activation and membrane vesicle trafficking. GST-SH3 domain pulldown, co-immunoprecipitation, [35S]methionine labeling Cellular signalling Medium 10206341
2012 c-ABL phosphorylates NCK1 at tyrosine 105 downstream of VEGFR-2/PI3K; this NCK1 phosphorylation mediates negative feedback on p38 MAP kinase signaling in endothelial cells. Co-immunoprecipitation, in vitro kinase assay, NCK1 mutant analysis, dominant-negative c-ABL, siRNA, MAP kinase activity assay Angiogenesis Medium 22327338
2019 TNK2, WASL (N-WASP), and NCK1 function in a common pathway for picornavirus (EMCV, CVB3, poliovirus, EV-D68) entry; genetic epistasis by CRISPR deletion and reduced EMCV internalization in TNK2-deficient cells confirm that NCK1 functions in viral entry through actin nucleation. CRISPR gene deletion, genetic epistasis (double/triple knockouts), viral internalization assay, chemical inhibitors eLife High 31769754
2015 NCK1 interacts with SOCS7 and is carried into the nucleus by SOCS7; the nuclear NCK-SOCS7 pool intersects with ATM/ATR signaling downstream to enable p53 Ser15 phosphorylation during DNA damage response. The septin-SOCS7-NCK axis is essential for cell-cycle arrest. Knockdown (siRNA) of septins/SOCS7, fractionation, rescue with cytoplasmic vs nuclear NCK, cell-cycle analysis Cell High 17803907
2016 Nck sequesters the adaptor WTIP and its binding partner Lats1 to phosphorylated nephrin via direct Nck-WTIP association, resulting in decreased Lats1 phospho-activation and suppressed Hippo signaling (YAP stabilization) in podocytes. Mutational analysis, co-immunoprecipitation, in vivo podocyte injury model (nephrin dephosphorylation), Lats1 and YAP western blotting The Journal of biological chemistry Medium 27033705

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 665 12181570
1997 Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130cas, and Nck adaptor proteins. Molecular and cellular biology 405 9032297
2001 Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway. The Journal of biological chemistry 335 11340081
2001 Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in host cells. Nature cell biology 298 11533668
1995 Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. Molecular and cellular biology 278 7565724
1996 Interaction of the Nck adapter protein with p21-activated kinase (PAK1). The Journal of biological chemistry 273 8824201
2006 Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization. The Journal of clinical investigation 269 16543952
2004 EspFU is a translocated EHEC effector that interacts with Tir and N-WASP and promotes Nck-independent actin assembly. Developmental cell 255 15296718
1993 Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells. Proceedings of the National Academy of Sciences of the United States of America 212 8265614
2007 Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell 181 17803907
2001 Evidence for a molecular complex consisting of Fyb/SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fcgamma receptor signalling during phagocytosis. Journal of cell science 164 11739662
2003 Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell migration. Molecular and cellular biology 150 14585966
2001 Nck/Dock: an adapter between cell surface receptors and the actin cytoskeleton. Oncogene 150 11607841
2004 The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. The Journal of biological chemistry 142 15342639
2015 Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck. Proceedings of the National Academy of Sciences of the United States of America 141 26553976
1998 Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. The Journal of biological chemistry 139 9430661
2010 Specific tyrosine phosphorylation sites on cortactin regulate Nck1-dependent actin polymerization in invadopodia. Journal of cell science 127 20971703
2002 Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus. Current biology : CB 125 12007418
2009 Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation. Journal of cell science 123 19596797
2002 Phosphatidylinositol 4,5-biphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck, WIP, and Grb2. The Journal of biological chemistry 123 12147689
2006 The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors. Proceedings of the National Academy of Sciences of the United States of America 111 16938849
2007 Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Biochemistry 108 17302440
1998 A Nck-Pak1 signaling module is required for T-cell receptor-mediated activation of NFAT, but not of JNK. The EMBO journal 105 9755165
1992 The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels. Molecular and cellular biology 101 1280326
2002 The adaptor protein Nck-1 couples the netrin-1 receptor DCC (deleted in colorectal cancer) to the activation of the small GTPase Rac1 through an atypical mechanism. The Journal of biological chemistry 94 12149262
2001 The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor. The Journal of biological chemistry 87 11369779
2008 Phosphorylated YDXV motifs and Nck SH2/SH3 adaptors act cooperatively to induce actin reorganization. Molecular and cellular biology 86 18212058
2006 The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains. The Journal of biological chemistry 83 16636066
1999 Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes. European journal of immunology 83 10229072
1998 The Nck SH2/SH3 adaptor protein: a regulator of multiple intracellular signal transduction events. BioEssays : news and reviews in molecular, cellular and developmental biology 83 9872057
2002 A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans. Current biology : CB 77 11967148
2001 Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK). Development (Cambridge, England) 76 11290295
2003 Nck beta interacts with tyrosine-phosphorylated disabled 1 and redistributes in Reelin-stimulated neurons. Molecular and cellular biology 74 14517291
1998 Identification of Nck family genes, chromosomal localization, expression, and signaling specificity. The Journal of biological chemistry 70 9737977
2012 Stoichiometry of Nck-dependent actin polymerization in living cells. The Journal of cell biology 66 22613834
2015 Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization. Circulation 64 26659946
1997 A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs. Biochemical and biophysical research communications 64 9344857
2006 Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B. Proceedings of the National Academy of Sciences of the United States of America 63 16769879
2013 WIP provides an essential link between Nck and N-WASP during Arp2/3-dependent actin polymerization. Current biology : CB 62 23707428
1997 A casein kinase I activity is constitutively associated with Nck. The Journal of biological chemistry 62 9006905
2006 The adaptor protein Nck interacts with Fas ligand: Guiding the death factor to the cytotoxic immunological synapse. Proceedings of the National Academy of Sciences of the United States of America 57 16595635
2001 Human immunodeficiency virus type 1 Nef selectively associates with a catalytically active subpopulation of p21-activated kinase 2 (PAK2) independently of PAK2 binding to Nck or beta-PIX. Journal of virology 55 11160719
2013 Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells. Nature immunology 52 23913047
2013 Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics. Nature communications 51 24287595
2011 Functional cooperation between the proteins Nck and ADAP is fundamental for actin reorganization. Molecular and cellular biology 51 21536650
2001 NCK and PAK participate in the signaling pathway by which vascular endothelial growth factor stimulates the assembly of focal adhesions. The Journal of biological chemistry 51 11278553
2009 Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo. Molecular microbiology 50 19889090
2007 Enterohaemorrhagic and enteropathogenic Escherichia coli Tir proteins trigger a common Nck-independent actin assembly pathway. Cellular microbiology 50 17521329
2013 Cdc42 and the Rho GEF intersectin-1 collaborate with Nck to promote N-WASP-dependent actin polymerisation. Journal of cell science 48 24284073
2002 Modulation of protein translation by Nck-1. Proceedings of the National Academy of Sciences of the United States of America 47 11959995
1997 Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac. The Biochemical journal 47 9148763
1995 A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain. The Journal of biological chemistry 47 7706279
2012 Direct regulation of nephrin tyrosine phosphorylation by Nck adaptor proteins. The Journal of biological chemistry 45 23188823
2001 SPIN90 (SH3 protein interacting with Nck, 90 kDa), an adaptor protein that is developmentally regulated during cardiac myocyte differentiation. The Journal of biological chemistry 45 11278500
2020 Long non-coding RNA NCK1-AS1 promotes the tumorigenesis of glioma through sponging microRNA-138-2-3p and activating the TRIM24/Wnt/β-catenin axis. Journal of experimental & clinical cancer research : CR 44 32293515
2008 A crucial role in cell spreading for the interaction of Abl PxxP motifs with Crk and Nck adaptors. Journal of cell science 44 18768933
2018 Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to cisplatin in cervical cancer. Journal of cellular physiology 42 30221354
2014 A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells. PloS one 41 25337707
2013 Nck enables directional cell migration through the coordination of polarized membrane protrusion with adhesion dynamics. Journal of cell science 41 23444376
2019 Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer. Journal of experimental & clinical cancer research : CR 40 30867003
2012 Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET. Science signaling 39 22534133
2010 Deletion of Nck1 attenuates hepatic ER stress signaling and improves glucose tolerance and insulin signaling in liver of obese mice. American journal of physiology. Endocrinology and metabolism 39 20587749
2006 Rat nephrin modulates cell morphology via the adaptor protein Nck. Biochemical and biophysical research communications 39 16934223
2001 Identification and kinetic analysis of the interaction between Nck-2 and DOCK180. FEBS letters 39 11240126
2010 The Gab1 scaffold regulates RTK-dependent dorsal ruffle formation through the adaptor Nck. Journal of cell science 37 20332103
2014 Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo. Journal of immunology (Baltimore, Md. : 1950) 36 24470497
2012 The adaptor molecule Nck localizes the WAVE complex to promote actin polymerization during CEACAM3-mediated phagocytosis of bacteria. PloS one 36 22448228
2015 The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit. The Journal of cell biology 34 25601402
2014 The cytoplasmic capping complex assembles on adapter protein nck1 bound to the proline-rich C-terminus of Mammalian capping enzyme. PLoS biology 34 25137142
2009 A reciprocal interdependence between Nck and PI(4,5)P(2) promotes localized N-WASp-mediated actin polymerization in living cells. Molecular cell 34 19917259
2004 Nck and Crk mediate distinct VEGF-induced signaling pathways that serve overlapping functions in focal adhesion turnover and integrin activation. Experimental cell research 34 15051508
1999 Characterization of interactions of Nck with Sos and dynamin. Cellular signalling 34 10206341
2007 Enteropathogenic Escherichia coli O125:H6 triggers attaching and effacing lesions on human intestinal biopsy specimens independently of Nck and TccP/TccP2. Infection and immunity 32 17984209
2017 Identification of NCK1 as a novel downstream effector of STAT3 in colorectal cancer metastasis and angiogenesis. Cellular signalling 31 28455144
1996 Hepatocyte growth factor induces activation of Nck and phospholipase C-gamma in lung carcinoma cells. Cancer letters 31 8665484
2019 Knockdown Of lncRNA NCK-AS1 Regulates Cisplatin Resistance Through Modulating miR-137 In Osteosarcoma Cells. OncoTargets and therapy 30 31908475
2012 c-ABL modulates MAP kinases activation downstream of VEGFR-2 signaling by direct phosphorylation of the adaptor proteins GRB2 and NCK1. Angiogenesis 30 22327338
2000 The SH2 and SH3 adapter Nck: a two-gene family and a linker between tyrosine kinases and multiple signaling networks. Histology and histopathology 30 10963137
2019 NCK1-AS1 Increases Drug Resistance of Glioma Cells to Temozolomide by Modulating miR-137/TRIM24. Cancer biotherapy & radiopharmaceuticals 29 31750728
2015 Allosteric N-WASP activation by an inter-SH3 domain linker in Nck. Proceedings of the National Academy of Sciences of the United States of America 29 26554011
2010 Traf2- and Nck-interacting kinase is essential for canonical Wnt signaling in Xenopus axis formation. The Journal of biological chemistry 29 20566648
1999 Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells. Oncogene 29 10597244
1997 Expression of mutated Nck SH2/SH3 adaptor respecifies mesodermal cell fate in Xenopus laevis development. Proceedings of the National Academy of Sciences of the United States of America 29 9114017
2013 Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration. Bioarchitecture 28 23887203
2001 Regulation of Cbl phosphorylation by the Abl tyrosine kinase and the Nck SH2/SH3 adaptor. Oncogene 28 11494134
2020 NCK1-AS1 enhances glioma cell proliferation, radioresistance and chemoresistance via miR-22-3p/IGF1R ceRNA pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 32887025
2012 EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak. Molecular and cellular neurosciences 27 23147113
2019 NCK1-AS1 promotes NCK1 expression to facilitate tumorigenesis and chemo-resistance in ovarian cancer. Biochemical and biophysical research communications 26 31761329
2015 Nck influences preosteoblastic/osteoblastic migration and bone mass. Proceedings of the National Academy of Sciences of the United States of America 26 26621720
2014 Non-overlapping functions of Nck1 and Nck2 adaptor proteins in T cell activation. Cell communication and signaling : CCS 26 24670066
2010 Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire. Proceedings of the National Academy of Sciences of the United States of America 25 20709959
2006 A novel category of enteropathogenic Escherichia coli simultaneously utilizes the Nck and TccP pathways to induce actin remodelling. Cellular microbiology 25 16681840
2015 Recruitment of the adaptor protein Nck to PECAM-1 couples oxidative stress to canonical NF-κB signaling and inflammation. Science signaling 24 25714462
1998 Characterization of Cbl-Nck and Nck-Pak1 interactions in myeloid FcgammaRII signaling. Experimental cell research 23 9851874
2019 Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion. Cancer medicine 22 31638742
2019 Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL, and NCK1. eLife 22 31769754
2018 Proteomic Analysis of NCK1/2 Adaptors Uncovers Paralog-specific Interactions That Reveal a New Role for NCK2 in Cell Abscission During Cytokinesis. Molecular & cellular proteomics : MCP 22 30002203
2018 NCK1 promotes the angiogenesis of cervical squamous carcinoma via Rac1/PAK1/MMP2 signal pathway. Gynecologic oncology 22 30442385
2016 Nephrin Suppresses Hippo Signaling through the Adaptor Proteins Nck and WTIP. The Journal of biological chemistry 22 27033705
2020 Selective role of Nck1 in atherogenic inflammation and plaque formation. The Journal of clinical investigation 21 32427580