Affinage

CRKL

Crk-like protein · UniProt P46109

Length
303 aa
Mass
33.8 kDa
Annotated
2026-04-28
100 papers in source corpus 58 papers cited in narrative 57 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRKL is an SH2-SH3-SH3 adaptor protein that serves as a central signaling hub downstream of diverse tyrosine kinases, coupling phosphotyrosine-containing docking proteins to guanine nucleotide exchange factors and effector pathways that control cell migration, adhesion, cytoskeletal organization, and transcription. Its SH2 domain binds phosphorylated substrates including p130CAS, CBL, HEF1, SHIP1, LASP1, STAT5, and FGFR1-pY463, while its N-terminal SH3 domain constitutively recruits exchange factors C3G, SOS1, and DOCK2 to activate RAP1, RAS-ERK, and RAC1/CDC42 pathways; its C-terminal SH3 domain mediates homodimerization that buries a nuclear export signal and binds CD34 (PMID:8361759, PMID:9162067, PMID:12393632, PMID:17161365, PMID:11389015). CRKL is the principal tyrosine-phosphorylated protein in BCR-ABL-positive leukemias, where phosphorylation at Y207 acts as a negative regulatory switch, and it is required for BCR-ABL-driven factor-independent growth and transformation through RAS, JNK, PI3K-AKT, and nuclear CrkL-STAT5 transcriptional complexes (PMID:8083188, PMID:9053848, PMID:20807813, PMID:9872990). In development, CRKL is essential for neural crest-derived craniofacial and cardiac outflow tract formation (interacting genetically with TBX1 in 22q11-related phenotypes), Reelin-Dab1-directed cortical neuron positioning, and MuSK/Dok-7-dependent neuromuscular synapse assembly via Sorbs1/2 recruitment (PMID:11242111, PMID:16399080, PMID:15062102, PMID:21041412, PMID:26527617). CRKL haploinsufficiency contributes to congenital heart defects associated with distal 22q11.2 deletions, and CRKL amplification drives oncogenic signaling and immune evasion in solid tumors through β-catenin stabilization and ERK-dependent invasion (PMID:25658046, PMID:38403027, PMID:22586683).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Cloning of CRKL established that chromosome 22q11 encodes a second CRK-family adaptor protein with an SH2-SH3-SH3 architecture but no catalytic domain, raising the question of its signaling role.

    Evidence cDNA cloning, sequencing, and chromosomal mapping

    PMID:8361759

    Open questions at the time
    • No binding partners or biological function identified
    • Relationship to v-crk transforming activity unknown
  2. 1994 High

    Identification of CRKL as the dominant tyrosine-phosphorylated species in BCR-ABL-positive CML established it as a key BCR-ABL substrate and implicated it in leukemogenesis.

    Evidence Anti-phosphotyrosine immunoblotting of CML patient neutrophils, microsequencing, yeast two-hybrid, co-immunoprecipitation across multiple labs

    PMID:7521685 PMID:7524758 PMID:8083188 PMID:8168080

    Open questions at the time
    • Phosphorylation sites on CRKL not mapped
    • Functional consequence of phosphorylation unknown
    • Mechanism of CRKL recruitment to BCR-ABL not resolved
  3. 1996 High

    Demonstration that CRKL overexpression activates RAS/JNK and transforms fibroblasts established CRKL as an active signaling molecule rather than a passive substrate, and identification of SH2 partners (p130CAS, CBL) placed CRKL at focal adhesion signaling nodes.

    Evidence Fibroblast transformation assay with RAS epistasis; reciprocal co-IP of p130CAS and CBL with CRKL-SH2 in patient samples; CBL phospho-site mutagenesis

    PMID:8649859 PMID:8798523 PMID:8810278

    Open questions at the time
    • SH3 domain effectors beyond SOS not characterized
    • Mechanism of RAS activation by CRKL unclear
  4. 1997 High

    Mapping Y207 as the major BCR-ABL phosphorylation site on CRKL, with the Y207F mutation enhancing rather than abolishing function, revealed phosphorylation as a negative regulatory switch and defined the intramolecular SH2-pY207 interaction as an autoinhibitory mechanism.

    Evidence Tryptic phosphopeptide mapping, site-directed mutagenesis, in vitro kinase assay, fibroblast transformation and JNK activation assays

    PMID:9053848 PMID:9710592

    Open questions at the time
    • Structural basis for autoinhibition not resolved at this point
    • In vivo relevance of Y207 phosphorylation not tested in animal models
  5. 1997 High

    Identification of the N-terminal SH3 domain as the hub for C3G, SOS, DOCK180, and ABL binding, and demonstration that CRKL recruits C3G to the membrane to activate Rap1 GEF activity, established the core adaptor mechanism by which CRKL couples upstream phosphotyrosine signals to GTPase activation.

    Evidence Domain-deletion mutants, GTP/GDP Rap1 assay with farnesylation rescue in COS1 cells, integrin-ligation co-IP in hematopoietic cells, peptide competition disrupting SH3 complexes

    PMID:9162067 PMID:9268367 PMID:9405482 PMID:9591773

    Open questions at the time
    • Relative contributions of C3G vs SOS vs DOCK pathways not dissected
    • In vivo requirement for individual SH3-partner interactions unknown
  6. 1999 High

    Functional studies showed that the CRKL–C3G axis is required for both integrin-mediated adhesion and hematopoietic cell migration, and that CRKL mediates cytokine (Epo/IL-3)-induced Ras-dependent ERK activation, unifying CRKL's role across adhesion and growth factor signaling.

    Evidence Transwell migration and adhesion assays with domain mutants and dominant-negative C3G; ERK/Elk-1 reporter with dominant-negative Ras epistasis; HPK1 synergy with JNK

    PMID:10339478 PMID:10514505 PMID:10608804 PMID:9891069

    Open questions at the time
    • Contribution of CRKL vs CrkII in these assays not genetically separated
    • In vivo relevance of C3G pathway not demonstrated
  7. 1999 High

    Discovery that IFNα-induced CrkL-Stat5 complexes translocate to the nucleus and bind GAS elements revealed an unexpected nuclear adaptor function for CRKL in transcription, extending its role beyond cytoplasmic signaling.

    Evidence Nuclear fractionation, EMSA with CrkL antibody supershift, co-IP of CrkL-Stat5, GST-SH2 binding to phospho-Stat5

    PMID:10720695 PMID:9872990

    Open questions at the time
    • Target gene set regulated by nuclear CrkL-Stat5 not comprehensively defined
    • Mechanism of nuclear import unknown
  8. 2001 High

    Crkl-null mice revealed an essential developmental role in neural crest differentiation, with defects in cardiac outflow tract, aortic arch arteries, thymus, and craniofacial structures, establishing CRKL as required for pharyngeal apparatus morphogenesis.

    Evidence Targeted null mutation in mice with systematic embryological analysis

    PMID:11242111

    Open questions at the time
    • Cell-autonomous vs non-autonomous role in neural crest not determined
    • Downstream signaling pathway in neural crest not identified
  9. 2003 High

    Demonstration that CRKL translocates to focal adhesions in a Src/Cas-dependent manner and that forced focal adhesion targeting is sufficient to activate Rac1/Cdc42 and rescue migration of Src-family null cells established CRKL as a spatial organizer of GTPase signaling at adhesion sites.

    Evidence CrkL-null and Src/Yes/Fyn-null MEFs, focal adhesion targeting constructs, Rac1/Cdc42 pulldown assays

    PMID:12522101 PMID:12665586

    Open questions at the time
    • DOCK1 vs DOCK2 contribution at focal adhesions not resolved
    • Regulation of CRKL exit from focal adhesions unknown
  10. 2004 High

    Placing CRKL in the Reelin→Dab1→CrkL→C3G→Rap1 pathway for cortical neuron migration explained how the adaptor function discovered in hematopoietic cells is repurposed in brain development.

    Evidence Phosphopeptide pulldown from embryonic brain lysates, Rap1 activation upon Reelin stimulation, Crkl-null epistasis

    PMID:15062102

    Open questions at the time
    • Relative contribution of CrkL vs CrkII in Reelin signaling not fully separated
    • Downstream effectors of Rap1 in neuronal migration not identified
  11. 2006 High

    Genetic interaction between Crkl and Tbx1 in compound-heterozygous mice, with rescue by reduced retinoic acid production, revealed the molecular pathway (RA metabolism) through which CRKL contributes to 22q11 deletion syndrome-like phenotypes.

    Evidence Compound heterozygous mouse genetics with retinoic acid pathway epistasis

    PMID:16399080

    Open questions at the time
    • Direct biochemical link between CRKL and RA metabolism not established
    • Whether CRKL acts cell-autonomously in pharyngeal endoderm vs neural crest not resolved
  12. 2006 High

    Crystal structure of the C-terminal SH3 domain dimer showed that dimerization buries a nuclear export signal, providing a structural mechanism for regulating CRKL nuclear-cytoplasmic distribution.

    Evidence X-ray crystallography and size-exclusion chromatography

    PMID:17161365

    Open questions at the time
    • Whether dimer-monomer transition is regulated by upstream signals in vivo not tested
    • NES-dependent export not validated by mutagenesis in cells
  13. 2010 High

    Identification of Dok-7 phosphotyrosines as docking sites for Crk/CrkL, and demonstration that muscle-specific double KO causes severe neuromuscular synapse defects, established CRKL as essential for postsynaptic differentiation at the neuromuscular junction.

    Evidence Dok-7 phospho-site mapping, co-IP, muscle-specific conditional KO mice

    PMID:21041412

    Open questions at the time
    • How CrkL connects Dok-7 to downstream AChR clustering machinery was unknown at this point
  14. 2012 High

    NMR structures revealed that despite high sequence identity, CrkL adopts a three-dimensional fold distinct from CrkII, with different autoinhibitory conformations upon phosphorylation, explaining why BCR-ABL preferentially uses CrkL.

    Evidence NMR spectroscopy with functional binding assays comparing phospho-CrkL and phospho-CrkII

    PMID:22581121

    Open questions at the time
    • Whether conformational differences apply in crowded intracellular conditions not tested
    • Full-length structure including linker regions not resolved
  15. 2015 High

    Identification of Sorbs1/2 as CrkL-binding proteins required for AChR clustering completed the Dok-7→Crk/CrkL→Sorbs1/2 module for neuromuscular synapse assembly.

    Evidence Mass spectrometry-based partner identification, co-IP, AChR clustering assay

    PMID:26527617

    Open questions at the time
    • Mechanism by which Sorbs proteins promote AChR clustering not defined
    • Whether this pathway operates in synapse maintenance vs initial formation unclear
  16. 2015 High

    An allelic dosage series demonstrated that CRKL is haploinsufficient for cardiac outflow tract formation, directly linking CRKL copy number to congenital heart defects in individuals with distal 22q11.2 deletions.

    Evidence Allelic series of Crkl mouse mutants including hypomorphic alleles with cardiac phenotype quantification

    PMID:25658046

    Open questions at the time
    • Whether CRKL haploinsufficiency alone is sufficient in humans or requires modifier loci unknown
    • Cell types mediating dose-sensitivity not identified
  17. 2017 High

    Demonstration that CRKL links Src-phosphorylated p130Cas specifically to the p110β isoform of PI3K in PTEN-null cancers revealed isoform-selective signaling through CRKL, expanding its role in oncogenic PI3K pathway activation.

    Evidence CRKL knockdown in PTEN-null cells with p110β-specific PI3K assay, co-IP with p130Cas, Src inhibitor epistasis

    PMID:28723560

    Open questions at the time
    • Whether this selectivity operates in non-cancer contexts unknown
    • Structural basis for p110β vs p110α selectivity not resolved
  18. 2024 High

    Discovery that CRKL stabilizes β-catenin by disrupting the Axin1-APC destruction complex, driving VEGFA/CXCL1 expression and neutrophil-mediated immune evasion in HCC, revealed a previously unrecognized non-canonical role for CRKL in Wnt pathway regulation and anti-PD-1 resistance.

    Evidence CRISPR-KO, co-IP of CRKL-Axin1-APC, mass cytometry, orthotopic HCC mouse model, patient-derived organotypic spheroids

    PMID:38403027

    Open questions at the time
    • Whether CRKL-Axin1 interaction requires CRKL SH2 or SH3 domains not mapped
    • Generalizability to other tumor types not established
    • Direct vs indirect binding to Axin1 not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for full-length CRKL autoinhibition, the tissue-specific balance between CrkL and CrkII redundancy, and whether the β-catenin stabilization mechanism operates outside hepatocellular carcinoma.
  • Full-length autoinhibited structure not available
  • Conditional tissue-specific KO comparisons of CrkL vs CrkII remain incomplete
  • In vivo significance of NES-masking dimerization not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 13 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-1266738 Developmental Biology 7 R-HSA-1643685 Disease 6 R-HSA-1500931 Cell-Cell communication 5 R-HSA-168256 Immune System 5
Partners
ABL1BCAR1C3GCBLDOCK2RAPGEF1SOS1STAT5A
Complex memberships
BCR-ABL-CrkL-CBL complexCrkL-C3G-Rap1 signaling moduleCrkL-STAT5 nuclear transcription complexDok-7-Crk/CrkL-Sorbs1/2 NMJ complex

Evidence

Reading pass · 57 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CRKL encodes an SH2-SH3-SH3 adapter protein (one SH2 and two SH3 domains, 303 amino acids, predicted 36 kDa) lacking any catalytic domain, mapping to chromosome 22q11, distinct from the human homolog of v-crk. cDNA cloning, sequencing, chromosomal localization Oncogene High 8361759
1994 CRKL is the major tyrosine-phosphorylated protein (39 kDa) in CML neutrophils and cell lines expressing p210BCR-ABL, identified by microsequencing of purified protein; direct interaction between CRKL and ABL demonstrated by yeast two-hybrid screen. Anti-phosphotyrosine immunoblotting, protein purification, microsequencing, yeast two-hybrid The Journal of biological chemistry High 7524758 8083188
1994 CRKL is a substrate for the p210BCR-ABL and p145 ABL tyrosine kinases; BCR/ABL and ABL co-immunoprecipitate with CRKL in vivo, forming stable complexes; the nucleotide exchange factor mSOS1 also co-immunoprecipitates with CRKL. Co-immunoprecipitation, in vitro kinase assay Cancer research High 8168080
1994 CRKL is tyrosine-phosphorylated in all BCR/ABL+ CML and Ph+ ALL patient samples examined but not in Ph-negative peripheral blood cells, establishing CRKL as a biologically significant substrate for BCR/ABL. Anti-phosphotyrosine immunoblotting of patient peripheral blood samples Blood High 7521685
1996 CRKL overexpression activates RAS and JUN kinase signaling pathways and transforms fibroblasts in a RAS-dependent fashion; CRKL contributes to BCR-ABL-mediated fibroblast transformation alongside GRB2, with the double adaptor mutant showing a 15-fold reduction in transforming activity. Fibroblast transformation assay, RAS activation assay, BCR-ABL deletion mutants The Journal of biological chemistry High 8798523
1996 p130CAS is tyrosine-phosphorylated and associated with CRKL via the CRKL-SH2 domain in BCR/ABL-expressing cells; BCR/ABL also disrupts the normal interaction of p130CAS with tensin while preserving CAS-FAK and CAS-paxillin associations. Co-immunoprecipitation, immunoblotting from patient samples and cell lines, immunofluorescence The Journal of biological chemistry High 8810278
1996 The two major tyrosine phosphorylation sites of CBL in ABL-transformed cells conform to the YXXP sequence and mediate association with the CRKL SH2 domain. Site-directed mutagenesis of CBL phosphorylation sites, GST pulldown with CRKL-SH2 Oncogene High 8649859
1997 Tyrosine 207 in CRKL is the major BCR/ABL phosphorylation site; Y207F mutation abolishes in vivo tyrosine phosphorylation; phospho-Y207 provides a binding site for the CRKL SH2 domain; Y207F mutation enhanced CRKL function (complex formation, JNK signaling, transformation), indicating Y207 phosphorylation is a negative regulatory event. In vitro kinase assay, site-directed mutagenesis, tryptic phosphopeptide mapping, fibroblast transformation assay Oncogene / Molecular and cellular biology High 9053848 9710592
1997 CRKL N-terminal SH3 domain binds directly to BCR-ABL proline-rich region; however, direct CRKL–BCR-ABL binding is not required for BCR-ABL transformation or for CRKL tyrosine phosphorylation, as CRKL can associate indirectly. Co-immunoprecipitation, gel overlay assay, yeast two-hybrid, proline-rich region deletion mutant of BCR-ABL Blood High 8978305
1997 After beta1 integrin ligation, CRKL SH2 domain mediates binding to tyrosine-phosphorylated p120(CBL) in MO7e cells and to p110(HEF1) in H9 lymphoid cells; CRKL is constitutively complexed to C3G, SOS, and c-ABL via its SH3 domains irrespective of integrin ligation. Co-immunoprecipitation, far western blotting, domain-deletion mutants The Journal of biological chemistry High 9162067
1997 Steel factor (SCF) activation of c-Kit induces CRKL tyrosine phosphorylation; CRKL associates with c-Kit indirectly through a complex containing p85(PI3K) and p120(CBL); CRKL N-terminal SH3 domain but not SH2 domain mediates association with c-Kit; far western blotting demonstrates direct CRKL–SH3 binding to p85(PI3K). Co-immunoprecipitation, far western blotting with GST-CRKL-SH3 fusion protein The Journal of biological chemistry High 9092574
1997 HEF1/Cas-L is tyrosine-phosphorylated in P190BCR/ABL leukemic cells and associates with CRKL SH2 domain; complexes of P190Bcr/Abl, CRKL, and HEF1 or p120(Cbl) exist in leukemic tissues. Co-immunoprecipitation, GST-SH2 pulldown from transgenic mouse leukemic tissue The Journal of biological chemistry High 9405482
1997 CBL interacts directly with the SH2 domain of BCR-ABL when CBL is tyrosine-phosphorylated; CRKL can mediate an indirect complex between CBL and BCR-ABL. Co-immunoprecipitation, domain deletion analysis The Journal of biological chemistry Medium 9195915
1997 CrkL (via its N-terminal SH3 domain) binds C3G and enhances C3G-mediated guanine nucleotide exchange on Rap1 primarily by recruiting C3G to the cell membrane, as demonstrated by requirement for both SH2 and SH3 domains and rescue by farnesylation signal addition. GTP/GDP ratio assay in COS1 cells, domain mutant analysis, farnesylation rescue experiment The Journal of biological chemistry High 9268367
1997 Type I IFN receptor-associated Tyk-2 kinase is responsible for IFNalpha-induced tyrosine phosphorylation of CrkL; phosphorylated CrkL associates with Tyk-2 and with C3G (via N-terminal SH3), linking the IFN receptor to the C3G-Rap1 pathway. Co-immunoprecipitation, in vitro kinase assay on anti-CrkL immunoprecipitates The Journal of biological chemistry High 9374471
1998 All SH2 and SH3 domains of CRKL are required for fibroblast transformation and hematopoietic cell adhesion; mutations at Y207 abolish all in vivo tyrosine phosphorylation but enhance CRKL biological activity, confirming Y207 as a negative regulatory site; Cbl and paxillin bind via SH2 domain; ABL, SOS, C3G bind via N-terminal SH3. Fibroblast transformation assay, adhesion assay, tryptic phosphopeptide mapping, domain mutant analysis Molecular and cellular biology High 9710592
1998 CrkL interacts with IRS-4 via both its SH2 and N-terminal SH3 domains in response to IGF-I signaling; this interaction is stronger than that of CrkII which uses only its SH2 domain, explaining differential signaling outcomes. Co-immunoprecipitation, domain mutant analysis in overexpressing cell lines The Journal of biological chemistry Medium 9614078
1998 Selective high-affinity peptides binding the N-terminal SH3 domain of CrkL disrupt preformed CrkL complexes with DOCK180, SOS, and C3G in a concentration-dependent manner. GST-fusion protein pulldown, peptide competition assay, in-solution precipitation Oncogene High 9591773
1999 CrkL N-terminal SH3 domain binds the guanine exchange factor C3G; the Cbl–CrkL–C3G complex promotes hematopoietic cell migration; both SH2 and N-terminal SH3 domains are required for CrkL-enhanced migration; overexpression of C3G alone also enhances migration. Transwell migration assay, GFP-tagged domain mutants, FACS sorting, co-immunoprecipitation The Journal of biological chemistry High 10608804
1999 CrkL overexpression enhances integrin-mediated adhesion to fibronectin through VLA-4 and VLA-5 in hematopoietic cells; the N-terminal SH3 domain is critical for this effect and acts via C3G guanine nucleotide exchange activity; the SH2 domain is partially required. Adhesion assay, antibody blocking, domain-deletion mutants, dominant-negative C3G mutant Blood High 10339478
1999 CrkL interacts with HPK1 (hematopoietic progenitor kinase 1) via HPK1 proline-rich motifs; CrkL and Crk synergize with HPK1 to activate JNK; HPK1 phosphorylates CrkL mainly on serine/threonine residues in vitro. In vitro binding, co-immunoprecipitation, JNK activation assay, in vitro kinase assay Molecular and cellular biology High 9891069
1999 CrkL mediates Epo- and IL-3-induced, Ras-dependent activation of the Raf/ERK pathway via the C3G guanine nucleotide exchange factor; both SH2 and N-terminal SH3 domains of CrkL are required; dominant-negative Ras blocks CrkL/C3G-enhanced Elk-1 activation. Reporter gene assay, ERK activation assay, dominant-negative Ras, domain-deletion mutants The Journal of biological chemistry High 10514505
1999 IFNalpha-induced CrkL-Stat5 complex translocates to the nucleus and binds the TTCTAGGAA palindromic element in promoters of a subset of IFN-stimulated genes; Tyk-2 is the kinase responsible, and tyrosine-phosphorylated Stat5 acts as a docking site for the CrkL SH2 domain. Co-immunoprecipitation, EMSA, nuclear fractionation, GST-CrkL binding assay The Journal of biological chemistry High 9872990
2000 In BCR-ABL-expressing cells, CrkL associates with tyrosine-phosphorylated Stat5; CrkL is found in the nucleus and in a Stat5/DNA complex; CrkL increases transcriptional activation from a Stat-responsive reporter dependent on Bcr-Abl kinase activity. Co-immunoprecipitation, EMSA, immunofluorescence, luciferase reporter assay, GST-CrkL pulldown Experimental hematology High 10720695
2000 SHIP1 forms a novel signaling complex with DOK1, PI3K, and CRKL in BCR/ABL-transformed cells; CRKL associates directly with SHIP1 via the CRKL SH2 domain; tyrosines 917 and 1020 in SHIP1 mediate interactions with DOK1 and are required for SHIP1-dependent regulation of migration. Co-immunoprecipitation, domain mutant analysis, migration assay The Journal of biological chemistry Medium 11031258
2001 CrkL is an adapter for WASP via its SH3 domain; CrkL also associates with Syk tyrosine kinase via both SH2 and SH3 domains; CrkL immunoprecipitates contain kinase-active Syk; WASP, CrkL, Syk, and Hic-5 are incorporated into the platelet cytoskeleton after aggregation. Co-immunoprecipitation, GST-domain pulldown, in vitro kinase assay, cytoskeletal fractionation Blood High 11313252
2001 CrkL associates with CD34 via its C-terminal SH3 domain (not SH2 or N-terminal SH3) in hematopoietic cells; this association is specific to CrkL and not shared by CrkII. GST pulldown with CD34 intracellular domain, co-immunoprecipitation, domain-specific fusion proteins Blood Medium 11389015
2001 CrkL is required for IFNalpha-dependent gene transcription via GAS elements through formation of CrkL:Stat5 DNA-binding complexes; CrkL N-terminal SH3 domain is required for IFNalpha-induced Rap1 activation via C3G; Tyk-2 and Jak-1 are both required for CrkL/Rap1 pathway activation. CrkL-/- mouse embryonic fibroblasts, reporter gene assay, dominant-negative Jak mutants, Rap1 activation assay Biochemical and biophysical research communications High 11866427
2001 Mice homozygous for a Crkl null mutation display defects in cranial and cardiac neural crest derivatives (cranial ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid, craniofacial structures) with normal early neural crest migration, indicating an essential role in neural crest differentiation/survival. Targeted null mutation, embryological analysis, neural crest migration studies Nature genetics High 11242111
2002 DOCK2 binds the N-terminal SH3 domain of CrkL via two separate regions; CrkL and DOCK2 co-localize with F-actin in Jurkat cells; CrkL-induced Rac1 activation is inhibited by a dominant-negative DOCK2 mutant, establishing a CrkL–DOCK2–Rac1 signaling axis in hematopoietic cells. Co-immunoprecipitation, in vitro pulldown, immunofluorescence co-localization, Rac1 activation assay Blood High 12393632
2003 CrkL translocates to focal adhesions in a Src-dependent and Cas-dependent manner; forced focal adhesion localization of CrkL is sufficient to activate Rac1 and Cdc42, recruit Dock1 to focal adhesions, and rescue haptotaxis defects of Src/Yes/Fyn triple-KO fibroblasts; CrkL-null MEFs show impaired integrin-induced migration despite Crk-II expression. CrkL-/- MEFs, Src-family triple-KO MEFs, focal adhesion targeting constructs, Rac1/Cdc42 activation assay, live migration assay Molecular and cellular biology High 12665586
2003 CrkL N-terminal SH3 domain interacts with ASAP1 (an ARF-GAP) in platelets; CrkL recruits ASAP1 to focal adhesions in a manner dependent on the CrkL SH2 domain; SH2-mutant CrkL fails to localize to focal adhesions and fails to recruit ASAP1. Pull-down with N-SH3 domain + mass spectrometry, immunofluorescence co-localization, domain mutant overexpression in COS7 cells The Journal of biological chemistry High 12522101
2004 In the Reelin signaling pathway, CrkL (and CrkI/II) bind tyrosine-phosphorylated Dab1 via two phosphorylation sites (Y220 and Y232) that are critical for cortical neuron positioning; CrkL also binds C3G, and Reelin stimulates C3G tyrosine phosphorylation and Rap1 activation, placing CrkL in the Dab1→CrkL→C3G→Rap1 pathway. Phosphopeptide pulldown from embryonic brain extract, co-immunoprecipitation, Rap1 activation assay, Crkl-/- epistasis Current biology High 15062102
2006 Compound heterozygosity of mouse Crkl and Tbx1 (homologs of 22q11 genes) produces a dose-dependent increase in DiGeorge syndrome-like phenotype; these two genes interact to control pharyngeal segmentation and local retinoic acid metabolism/signaling; partial rescue achieved by reducing RA production genetically. Compound heterozygous mouse genetics, embryological analysis, genetic epistasis with retinoic acid pathway Developmental cell High 16399080
2006 The C-terminal SH3 domain of CRKL forms homodimers (confirmed in protein crystals and in solution), burying a nuclear export signal (NES); partial domain unfolding upon dimer/monomer transition exposes the NES, suggesting the SH3C dimer/monomer equilibrium regulates nuclear export of CRKL. X-ray crystallography, solution biochemistry (size-exclusion chromatography), NES analysis Structure High 17161365
2007 The N-terminal SH3 domain of CrkL (and Crk) is the preferred binding partner for the SH3-binding motif of NS1 proteins from the 1918 pandemic influenza and avian H7N3 viruses; this interaction enhances PI3K signaling (increased Akt phosphorylation) in infected/transfected cells. Phage display SH3 library screening, recombinant protein binding assay, co-immunoprecipitation from infected cells, Akt phosphorylation assay The Journal of biological chemistry High 18165234
2008 MUC1 ligation of ICAM-1 triggers formation of a Src–CrkL signaling complex at the MUC1 cytoplasmic domain; Src-dependent recruitment of CrkL to MUC1 is required for downstream Rac1/Cdc42 activation and actin cytoskeletal protrusive activity. Co-immunoprecipitation, Src kinase inhibition, actin reorganization assay Molecular cancer research Medium 18403635
2008 WAVE2 complex recruits Abl kinase to the membrane upon TCR ligation; Abl-dependent tyrosine phosphorylation of C3G activates its GEF activity toward Rap1; CrkL-C3G complex is recruited to the membrane by WAVE2 independently of Abl; this WAVE2–Abl–CrkL–C3G–Rap1 pathway regulates integrin clustering and affinity maturation in T cells. Co-immunoprecipitation, membrane fractionation, Rap1 activation assay, CrkL knockdown The Journal of cell biology High 18809728
2008 Reelin-induced dendritogenesis in hippocampal neurons is blocked by reducing Crk and CrkL expression via retroviral shRNA; this effect is Dab1-Src family kinase-dependent; CrkL knockdown does not affect BDNF-induced dendritogenesis or axonogenesis, demonstrating pathway specificity. Retroviral shRNA knockdown in primary neurons, dendrite morphometry, pathway specificity controls Journal of cell science High 18477607
2009 CRKL is required for FGF8 signaling: the CRKL SH2 domain binds specifically to phospho-Y463 of FGFR1 with ~30-fold higher affinity than CRK-SH2; CRKL functions in an FGF8-induced feed-forward loop for ERK1/2 activation and anchorage-independent growth, demonstrated in Crkl-deficient cells and with pY463 synthetic peptide competition. Molecular dynamics modeling, in vitro binding assay with phosphopeptides, Crkl-null cells, synthetic peptide inhibition, anchorage-independent growth assay Molecular and cellular biology High 19307307
2009 NKG2D signaling activates CrkL via PI3K (p85 regulatory subunit interacts with CrkL); CrkL depletion impairs NK cell-target conjugate formation, MTOC polarization toward target cells, and granule secretion; Rap1 is activated downstream of NKG2D in a PI3K- and CrkL-dependent manner. CrkL knockdown in NK cells, conjugate formation assay, MTOC polarization assay, granule release assay, Rap1 activation assay Journal of immunology High 19454690
2010 Agrin stimulation phosphorylates two tyrosine residues in the C-terminal domain of Dok-7, recruiting Crk and CrkL; selective inactivation of Crk and CrkL in skeletal muscle causes severe defects in neuromuscular synapse formation in vivo. Phosphorylation mapping of Dok-7 tyrosines, co-immunoprecipitation, muscle-specific conditional KO in mice Genes & development High 21041412
2010 CRKL is specifically required for p210BCR-ABL-induced IL-3-independent growth of myeloid progenitors and long-term B-lymphoid outgrowth; a synthetic phosphotyrosyl peptide binding the CRKL SH2 domain blocks CRKL association with the p210BCR-ABL complex and reduces c-MYC levels. Crkl-/- fetal liver hematopoietic progenitors, factor-independent growth assay, synthetic phosphopeptide inhibition, c-MYC western blot Cancer research High 20807813
2011 CRKL amplification and overexpression in NSCLC activates the SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways; CRKL overexpression induces gefitinib resistance by activating ERK and AKT signaling; CRKL-amplified cells are dependent on CRKL for survival. CRKL overexpression in airway epithelial cells, shRNA knockdown in amplified NSCLC lines, pathway activation western blot, gefitinib resistance assay Cancer discovery High 22586683
2012 CrkL and CrkII have markedly different three-dimensional structures (despite high sequence identity); phosphorylated CrkL adopts a distinct conformation from phospho-CrkII leading to different regulation of SH2 and SH3 domain binding activities; CrkL forms a constitutive complex with Abl kinase, explaining BCR-ABL's strong preference for CrkL over CrkII. NMR spectroscopy, functional binding assays, domain interaction studies Nature chemical biology High 22581121
2013 Combined loss of Crk and CrkL from fibroblasts results in reduced focal adhesions, actin stress fibers, microtubule collapse, and decreased motility; reduced p130Cas phosphorylation accompanies loss; CrkII partially rescues morphology; individual loss of either Crk or CrkL gives modest phenotype indicating overlapping functions. Conditional KO fibroblasts, morphological analysis, focal adhesion quantification, actin/microtubule staining, motility assay, p130Cas phospho-western Oncogene High 24166500
2013 CRKL is associated with YES (SRC family) kinase in rhabdomyosarcoma; CRKL expression is required for RMS growth in vitro and in vivo; loss-of-function screen identified CRKL as necessary for alveolar and embryonal RMS survival. Inducible shRNA loss-of-function screen, co-immunoprecipitation with YES, in vivo tumor growth assay Oncogene Medium 23318429
2014 CrkL overexpression promotes lung cancer cell invasion through ERK-MMP9 pathway; CrkL activates AP-1 (c-fos), ERK phosphorylation, and c-fos binding to MMP9 promoter; ERK inhibitor PD98059 blocks CrkL-induced invasion and MMP9 expression. Plasmid overexpression, western blot, ChIP assay, luciferase reporter, Matrigel invasion assay, ERK inhibitor Molecular carcinogenesis Medium 24664993
2014 CrkL and Crk2 form a hetero-oligomer; both are recruited to tyrosine-phosphorylated nephrin; CrkL is required for nephrin-induced lamellipodia formation in podocytes; podocyte-specific double deletion of Crk1/2 and CrkL causes albuminuria and altered foot process architecture. Podocyte-specific conditional KO mice, co-immunoprecipitation with nephrin, lamellipodia formation assay Kidney international High 24499776
2014 LASP1 is phosphorylated by BCR-ABL at tyrosine-171 in CML patients; phospho-LASP1-Y171 binds to the SH2 domain of non-phosphorylated CRKL, establishing LASP1 as a phosphorylation-dependent CRKL-SH2 binding partner in CML. Mass spectrometry, phospho-site mutagenesis, co-immunoprecipitation, in vitro binding assay with domain mapping Oncotarget High 24913448
2015 Sorbs1 and Sorbs2 associate with CrkL and are required for acetylcholine receptor (AChR) clustering; identified as CrkL-binding proteins by mass spectrometry; Sorbs1/2 participate downstream of the MuSK/Dok-7/Crk/CrkL complex for neuromuscular endplate formation. Mass spectrometry-based CrkL binding partner identification, co-immunoprecipitation, AChR clustering assay Molecular and cellular biology High 26527617
2015 Crkl is dosage-sensitive for cardiac outflow tract formation; an allelic series of Crkl mouse mutants demonstrates that the spectrum and penetrance of heart defects depends on Crkl expression level, with CRKL haploinsufficiency contributing to conotruncal defects in individuals with distal 22q11.2 deletions lacking TBX1. Allelic series of Crkl mouse mutants including hypomorphic allele, cardiac phenotype quantification American journal of human genetics High 25658046
2016 miR-200/Zeb1-EMT axis derepresses CRKL as a direct miR-200 target; CRKL acts as an adaptor facilitating focal adhesion formation and mediating outside-in integrin β1/FAK signaling to drive invasion and inside-out signaling maintaining tumor-matrix contacts; CRKL knockdown suppresses experimental metastasis in vivo. miR-200 overexpression, CRKL KD, 3D invasion assay, in vivo metastasis model, FAK/Src pathway western blot Scientific reports Medium 26728244
2017 CRKL mediates p110β-dependent PI3K signaling in PTEN-null cancer cells; CRKL binds tyrosine-phosphorylated p130Cas (promoted by Src) and links it to p110β; CRKL silencing decreases p110β-dependent signaling and cell proliferation without affecting p110α-mediated signaling. CRKL knockdown in PTEN-null cancer cells, p110β-specific PI3K assay, co-immunoprecipitation with p130Cas, Src inhibitor epistasis Cell reports High 28723560
2017 Crkl homozygous null mice exhibit upper genitourinary (kidney/ureter) defects; Crkl heterozygous adult males show cryptorchidism, reduced sperm count, and subfertility; RNA-seq of Crkl mutant kidneys reveals 52 differentially regulated genes including 5-fold upregulation of Foxd1. Crkl mutant mouse series, urogenital dissection, RNA-sequencing, fertility phenotyping PNAS High 28439006
2018 SASH1 tumor suppressor interacts directly with CRKL (identified by yeast two-hybrid and confirmed by co-immunoprecipitation); SASH1 inhibits CRKL-mediated SRC kinase activation; SASH1-deficient cells show increased invasion entirely dependent on CRKL. Yeast two-hybrid, co-immunoprecipitation, mass spectrometry, domain mapping, site-directed mutagenesis, dynamic mass redistribution assay, orthotopic mouse metastasis model Cellular and molecular gastroenterology and hepatology High 30480076
2024 CRKL inhibits APC-mediated proteasomal degradation of β-catenin by competitively reducing Axin1 binding to APC; this stabilizes β-catenin and promotes VEGFα and CXCL1 expression, driving tumor-associated neutrophil infiltration that blocks CD8+ T cell function and confers anti-PD-1 resistance in HCC. CRISPR-KO of CRKL, co-immunoprecipitation (CRKL-Axin1-APC), mass cytometry, orthotopic HCC mouse model, patient-derived organotypic tumor spheroid model Journal of hepatology High 38403027

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome. Nature genetics 238 11242111
2009 Crk and CrkL adaptor proteins: networks for physiological and pathological signaling. Cell communication and signaling : CCS 224 19426560
1994 Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia. The Journal of biological chemistry 221 8083188
1993 Isolation and chromosomal localization of CRKL, a human crk-like gene. Oncogene 214 8361759
1994 Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells. Blood 186 7524758
1994 Tyrosine phosphorylation of CRKL in Philadelphia+ leukemia. Blood 185 7521685
2004 Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Current biology : CB 165 15062102
2006 Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Developmental cell 162 16399080
1996 The CRKL adaptor protein transforms fibroblasts and functions in transformation by the BCR-ABL oncogene. The Journal of biological chemistry 122 8798523
1994 Cellular interactions of CRKL, and SH2-SH3 adaptor protein. Cancer research 122 8168080
2011 Amplification of CRKL induces transformation and epidermal growth factor receptor inhibitor resistance in human non-small cell lung cancers. Cancer discovery 121 22586683
1996 p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene. The Journal of biological chemistry 117 8810278
1999 Activation of a CrkL-stat5 signaling complex by type I interferons. The Journal of biological chemistry 114 9872990
1997 Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL). The Journal of biological chemistry 100 9092574
1996 The two major sites of cbl tyrosine phosphorylation in abl-transformed cells select the crkL SH2 domain. Oncogene 99 8649859
1998 Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR/ABL-transformed cells. Leukemia 98 9593259
1999 The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration. The Journal of biological chemistry 95 10608804
2010 Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes & development 92 21041412
1997 Enhancement of guanine-nucleotide exchange activity of C3G for Rap1 by the expression of Crk, CrkL, and Grb2. The Journal of biological chemistry 91 9268367
2007 Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling. The Journal of biological chemistry 87 18165234
2008 The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1. The Journal of cell biology 84 18809728
1997 Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1). The Journal of biological chemistry 84 9162067
1997 The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. The Journal of biological chemistry 84 9374471
2002 Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules. Molecular and cellular biology 82 12446789
1999 CrkL activates integrin-mediated hematopoietic cell adhesion through the guanine nucleotide exchange factor C3G. Blood 81 10339478
1999 Interaction of hematopoietic progenitor kinase 1 with adapter proteins Crk and CrkL leads to synergistic activation of c-Jun N-terminal kinase. Molecular and cellular biology 77 9891069
1997 Tyrosine 207 in CRKL is the BCR/ABL phosphorylation site. Oncogene 77 9053848
2008 Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis. Journal of cell science 73 18477607
1997 Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation. Blood 72 8978305
1998 Development of highly selective SH3 binding peptides for Crk and CRKL which disrupt Crk-complexes with DOCK180, SoS and C3G. Oncogene 68 9591773
2009 Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer. Oncogene 66 19966867
2006 BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry. Leukemia 65 16572205
1998 Structural requirements for function of the Crkl adapter protein in fibroblasts and hematopoietic cells. Molecular and cellular biology 65 9710592
2003 Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases. Molecular and cellular biology 63 12665586
2002 DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines. Blood 63 12393632
1997 Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. The Journal of biological chemistry 63 9195915
2008 MUC1 initiates Src-CrkL-Rac1/Cdc42-mediated actin cytoskeletal protrusive motility after ligating intercellular adhesion molecule-1. Molecular cancer research : MCR 59 18403635
2016 The microRNA-200/Zeb1 axis regulates ECM-dependent β1-integrin/FAK signaling, cancer cell invasion and metastasis through CRKL. Scientific reports 58 26728244
2015 Mouse and human CRKL is dosage sensitive for cardiac outflow tract formation. American journal of human genetics 58 25658046
1999 CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3. The Journal of biological chemistry 51 10514505
1998 Interleukin-2 stimulation induces tyrosine phosphorylation of p120-Cbl and CrkL and formation of multimolecular signaling complexes in T lymphocytes and natural killer cells. The Journal of biological chemistry 51 9461587
2012 Domain organization differences explain Bcr-Abl's preference for CrkL over CrkII. Nature chemical biology 50 22581121
2024 CRKL dictates anti-PD-1 resistance by mediating tumor-associated neutrophil infiltration in hepatocellular carcinoma. Journal of hepatology 49 38403027
2018 miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition. Scientific reports 49 29403024
2015 CrkL meditates CCL20/CCR6-induced EMT in gastric cancer. Cytokine 49 26044596
2009 PI3K links NKG2D signaling to a CrkL pathway involved in natural killer cell adhesion, polarity, and granule secretion. Journal of immunology (Baltimore, Md. : 1950) 49 19454690
2003 CrkL directs ASAP1 to peripheral focal adhesions. The Journal of biological chemistry 49 12522101
2017 The long noncoding RNA PCAT-1 links the microRNA miR-215 to oncogene CRKL-mediated signaling in hepatocellular carcinoma. The Journal of biological chemistry 48 28887306
1996 Crkl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemia patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin. Blood 48 8943867
2000 SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL. The Journal of biological chemistry 47 11031258
1997 BCR/ABL-induced leukemogenesis causes phosphorylation of Hef1 and its association with Crkl. The Journal of biological chemistry 46 9405482
2000 CrkL functions as a nuclear adaptor and transcriptional activator in Bcr-Abl-expressing cells. Experimental hematology 43 10720695
1997 Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells. Biochemical and biophysical research communications 43 9344843
2013 CRKL promotes cell proliferation in gastric cancer and is negatively regulated by miR-126. Chemico-biological interactions 42 24055140
2017 HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL. Biochemical pharmacology 41 29155146
2013 Loss-of-function screen in rhabdomyosarcoma identifies CRKL-YES as a critical signal for tumor growth. Oncogene 41 23318429
2018 The Tumor Suppressor SASH1 Interacts With the Signal Adaptor CRKL to Inhibit Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer. Cellular and molecular gastroenterology and hepatology 40 30480076
2014 CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway. Molecular carcinogenesis 40 24664993
2001 CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk. Blood 40 11313252
2017 CRKL Mediates p110β-Dependent PI3K Signaling in PTEN-Deficient Cancer Cells. Cell reports 39 28723560
2012 Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1. American journal of medical genetics. Part A 39 22318985
2006 The C-terminal SH3 domain of CRKL as a dynamic dimerization module transiently exposing a nuclear export signal. Structure (London, England : 1993) 39 17161365
1998 Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. The Journal of biological chemistry 39 9614078
2016 The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 27133071
2017 Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive regulator of genitourinary development. Proceedings of the National Academy of Sciences of the United States of America 37 28439006
2001 The adapter protein CrkL associates with CD34. Blood 36 11389015
2001 CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling. The Journal of biological chemistry 36 11443118
1997 The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins. Leukemia 36 9067577
2014 Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis. Kidney international 35 24499776
1997 Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells. Leukemia & lymphoma 35 9498705
1995 Tyrosine phosphorylation of murine Crkl. Oncogene 35 7478571
2021 Crk and CrkL as Therapeutic Targets for Cancer Treatment. Cells 34 33801580
2001 Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells. British journal of haematology 34 11167825
2008 Phospho-CRKL monitoring for the assessment of BCR-ABL activity in imatinib-resistant chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia patients treated with nilotinib. Haematologica 33 18367481
2013 Essential roles of Crk and CrkL in fibroblast structure and motility. Oncogene 30 24166500
2010 A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors. Cancer research 30 20807813
2002 The CrkL adapter protein is required for type I interferon-dependent gene transcription and activation of the small G-protein Rap1. Biochemical and biophysical research communications 30 11866427
2015 Sorbs1 and -2 Interact with CrkL and Are Required for Acetylcholine Receptor Cluster Formation. Molecular and cellular biology 29 26527617
1997 Inhibition of Grb2 and Crkl proteins results in growth inhibition of Philadelphia chromosome positive leukemic cells. Biochemical and biophysical research communications 29 9199202
1999 Involvement of the adapter protein CRKL in integrin-mediated adhesion. Oncogene 28 10362355
1998 Thrombopoietin induces association of Crkl with STAT5 but not STAT3 in human platelets. Blood 28 9845531
2019 CRKL regulates alternative splicing of cancer-related genes in cervical cancer samples and HeLa cell. BMC cancer 27 31133010
2015 CRKL oncogene is downregulated by p53 through miR-200s. Cancer science 27 26079153
2013 Overexpression of CRKL correlates with malignant cell proliferation in breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 23686806
1997 In vivo regulation of CrkII and CrkL proto-oncogenes in the uterus by insulin-like growth factor-I. Differential effects on tyrosine phosphorylation and association with paxillin. The Journal of biological chemistry 27 9346905
2019 MicroRNA-429 inhibits bone metastasis in breast cancer by regulating CrkL and MMP-9. Bone 26 31706051
2020 miR-124-3p Suppresses the Invasiveness and Metastasis of Hepatocarcinoma Cells via Targeting CRKL. Frontiers in molecular biosciences 25 33094104
2013 CrkL efficiently mediates cell proliferation, migration, and invasion induced by TGF-β pathway in glioblastoma. Journal of molecular neuroscience : MN 25 23959425
2009 Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop. Molecular and cellular biology 25 19307307
2002 BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl. Oncogene 25 12082638
2020 Bidirectional interaction of lncRNA AFAP1-AS1 and CRKL accelerates the proliferative and metastatic abilities of hepatocarcinoma cells. Journal of advanced research 24 32280542
2006 Active (p)CrkL is overexpressed in human malignancies: potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition. Oncology reports 24 16391854
2006 CrkL plays a role in SDF-1-induced activation of the Raf-1/MEK/Erk pathway through Ras and Rac to mediate chemotactic signaling in hematopoietic cells. Cellular signalling 24 16781119
2000 Engagement of the CrkL adapter in interleukin-5 signaling in eosinophils. The Journal of biological chemistry 24 10926930
2012 Modeling of molecular interaction between apoptin, BCR-Abl and CrkL--an alternative approach to conventional rational drug design. PloS one 22 22253690
2012 The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer. Journal of translational medicine 22 22591714
2011 Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma. Molecular carcinogenesis 22 21319228
2009 A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice. PloS one 22 19823681
2014 LASP1 is a novel BCR-ABL substrate and a phosphorylation-dependent binding partner of CRKL in chronic myeloid leukemia. Oncotarget 21 24913448
2006 Detection in primary chronic myeloid leukaemia cells of p210BCR-ABL1 in complexes with adaptor proteins CBL, CRKL, and GRB2. Genes, chromosomes & cancer 21 16955467