Affinage

PTK6

Protein-tyrosine kinase 6 · UniProt Q13882

Length
451 aa
Mass
51.8 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTK6 (BRK) is an intracellular non-receptor tyrosine kinase that integrates growth-factor signaling with control of cell proliferation, migration, survival, and epithelial-mesenchymal transition, with its subcellular localization acting as the key switch between tumor-suppressive and oncogenic outputs (PMID:19304789, PMID:20026641, PMID:23856248). The kinase is held in an autoinhibited conformation by intramolecular contacts: an SH3-domain interaction with the SH2-kinase linker (via W44 and linker prolines P175/P177/P179) and an SH2-domain engagement of C-terminal phospho-Y447, with activation requiring autophosphorylation of the activation-loop Y342 (PMID:12121988, PMID:17822667). This autoinhibition is biologically reinforced and reversed by opposing phosphatases and partners: PTEN and PTP1B directly dephosphorylate the activating Y342 to restrain PTK6, whereas ErbB2/HER2 interaction increases its intrinsic kinase activity and stabilizes the protein (PMID:29142193, PMID:23814047, PMID:18719096, PMID:23707532). Cancer-associated mutations in the SH3, SH2, and C-terminal tail disrupt these autoinhibitory contacts and constitutively activate the enzyme (PMID:25940761). In the nucleus, PTK6 phosphorylates RNA-binding proteins—Sam68, SLM-1/2, PSF, and HNRNPH1—to suppress their RNA-binding and redirect splicing and phase separation, and it antagonizes beta-catenin/TCF transcription (PMID:10913193, PMID:15471878, PMID:19439179, PMID:40103198, PMID:20026641). At the membrane and in the cytoplasm, PTK6 phosphorylates paxillin, Eps8, AKT, FAK, p130CAS, ARAP1, and beta-catenin and degrades the c-Cbl, Dok1, and SMAD4 tumor suppressors to drive motility, EGFR signaling sustainment, proliferation, survival, and EMT (PMID:15572663, PMID:28214294, PMID:23398121, PMID:20554524, PMID:22231447, PMID:23352614, PMID:24523872, PMID:31681835). Distinct domains carry distinct functions independent of catalysis—the SH2 domain mediates motility and the SH3 domain mediates spheroid formation—and kinase activity is dispensable for several growth-promoting phenotypes (PMID:33172975, PMID:29879184). PTK6 promotes EMT and metastasis by stabilizing SNAIL and repressing E-cadherin, and its nuclear retention by partners such as PSPC1 suppresses these metastatic functions (PMID:27302163, PMID:31844057). PTK6 is also druggable, with crystal structures and selective inhibitors defining its ATP pocket (PMID:27993680).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1994 Medium

    Established PTK6 as a novel SH3/SH2-containing non-receptor tyrosine kinase capable of autophosphorylation, defining its basic enzymatic identity.

    Evidence Recombinant expression in baculovirus and bacterial systems with autophosphorylation assay

    PMID:8036022

    Open questions at the time
    • No cellular substrates identified
    • No regulatory mechanism for activity defined
  2. 1996 Medium

    Separated the catalytic requirement from a regulatory tyrosine, showing kinase activity (K219) is essential for transformation while the C-terminal Y447 modulates transforming potential without abolishing catalysis.

    Evidence Site-directed mutagenesis with transformation assays in mammary epithelial cells

    PMID:8940083

    Open questions at the time
    • Mechanism by which Y447 regulates activity not resolved
    • No structural basis defined
  3. 2002 High

    Defined the molecular logic of PTK6 activation, identifying Y342 activation-loop autophosphorylation as activating and Y447–SH2 and SH3 contacts as autoinhibitory.

    Evidence Baculovirus expression, mass spectrometry phosphosite mapping, mutagenesis, and in vitro kinetics

    PMID:12121988

    Open questions at the time
    • Upstream activators in cells not identified
    • Structural model of autoinhibited state not solved
  4. 2007 High

    Mapped the SH3–linker autoinhibitory contact at residue level (W44 with linker prolines), explaining how intramolecular conformation restrains catalysis.

    Evidence Mutagenesis, surface plasmon resonance, kinase assays, and structural modeling

    PMID:17822667

    Open questions at the time
    • No full-length crystal structure of autoinhibited PTK6
    • Physiological trigger of release unclear
  5. 2000 High

    Identified nuclear RNA-binding proteins as the first physiological substrates, showing PTK6 phosphorylates Sam68 to abolish its RNA binding.

    Evidence Reciprocal co-IP, domain mapping, and functional RNA-binding assays across cell lines

    PMID:10913193

    Open questions at the time
    • In vivo relevance of Sam68 regulation not yet established
    • Downstream splicing consequences not mapped
  6. 2003 Medium

    Extended the Sam68 model to a functional consequence, showing PTK6-mediated hyperphosphorylation impairs Sam68-dependent intron-containing RNA utilization.

    Evidence Co-expression in 293T cells with RNA utilization assays and RNA-binding-defective Sam68 mutant

    PMID:12482964

    Open questions at the time
    • Endogenous target transcripts not identified
    • Physiological setting untested
  7. 2004 High

    Broadened the nuclear substrate repertoire and linked substrate phosphorylation to PTK6 nuclear retention, while demonstrating the SH3 domain dominates substrate recognition.

    Evidence Phosphorylation and RNA-binding assays for SLM-1/2 with selectivity controls; peptide kinetics linking SH3 to substrate Km

    PMID:14676834 PMID:15471878

    Open questions at the time
    • Determinants of nuclear vs cytoplasmic partitioning incompletely defined
  8. 2004 High

    Established the cytoplasmic migratory arm of PTK6 function, identifying paxillin phosphorylation driving Rac1 activation and cell motility upon EGF stimulation.

    Evidence Co-IP, in vitro kinase assay with phosphosite mapping, Rac1 activation, migration/invasion assays, and confocal localization

    PMID:15572663

    Open questions at the time
    • In vivo migration relevance not addressed
    • Mechanism of membrane translocation not defined
  9. 2000 Medium

    Connected PTK6 to growth-factor receptor signaling through adaptor proteins, identifying STAP-2/BKS and ErbB3/PI3K/AKT potentiation.

    Evidence Yeast two-hybrid, co-IP, and signaling assays (phospho-erbB3, PI3K recruitment, AKT)

    PMID:10980601 PMID:11114724

    Open questions at the time
    • Endogenous significance of adaptor interactions limited
    • Pathway integration with other receptors unclear
  10. 2009 Medium

    Demonstrated that PTK6 subcellular localization dictates opposing biological outcomes, with membrane-targeted PTK6 oncogenic and nuclear-targeted PTK6 growth-suppressive.

    Evidence Engineered Myr/NLS targeting constructs with functional and phosphoproteome profiling

    PMID:19304789

    Open questions at the time
    • Mechanism controlling localization in cells not resolved
    • Distinct substrate sets only partially characterized
  11. 2009 High

    Established PTK6 as a direct negative regulator of beta-catenin/TCF transcription, phosphorylating beta-catenin and showing localization-dependent transcriptional effects in vivo.

    Evidence In vitro kinase assay with phosphosite mapping, reporter assays, siRNA, and Ptk6-null BAT-GAL reporter mice

    PMID:20026641

    Open questions at the time
    • Mechanism linking phosphorylation to TCF/TLE repressor levels incompletely defined
  12. 2009 High

    Defined STAP-2 and PSF/cell-cycle nodes as PTK6 effectors, linking the kinase to STAT3 activation and to cell cycle arrest via impaired PSF RNA binding.

    Evidence Phosphosite-specific antibody and siRNA for STAP-2 Y250; proteomic MS, phosphosite mapping, and cell cycle analysis for PSF

    PMID:19393627 PMID:19439179

    Open questions at the time
    • Reconciliation of growth-suppressive (PSF) and growth-promoting outputs not addressed
  13. 2008 High

    Connected PTK6 amplification to HER2/ErbB2-driven breast cancer, showing ErbB2 activates PTK6 and PTK6 confers lapatinib resistance.

    Evidence Co-IP, FISH, 3D acini, WAP-Brk transgenic mice, and kinase assays

    PMID:18719096

    Open questions at the time
    • Direct phosphorylation events downstream of the ErbB2-PTK6 interaction not all mapped
  14. 2012 High

    Revealed that PTK6 sustains EGFR signaling by directly phosphorylating EGFR Y845 and uncoupling it from c-Cbl-mediated degradation.

    Evidence Co-IP, ubiquitination assay, in vitro kinase assay for phospho-Y845, and EGFR degradation assay

    PMID:22231447

    Open questions at the time
    • In vivo contribution to EGFR-driven tumors not quantified
  15. 2013 Medium

    Established phosphatase control of PTK6 (PTP1B) and direct degradation of tumor suppressors c-Cbl, situating PTK6 as a hub that destabilizes negative regulators.

    Evidence PTP1B re-expression with dephosphorylation/apoptosis assays; c-Cbl phosphosite mutagenesis and ubiquitination/proteasome assays

    PMID:23352614 PMID:23814047

    Open questions at the time
    • Relative contribution of c-Cbl degradation versus EGFR uncoupling unclear
  16. 2013 High

    Defined the membrane-localized active PTK6 pool as the metastatic driver in prostate cancer, identifying AKT/FAK/p130CAS substrates and EMT promotion in PTEN-null models.

    Evidence Subcellular fractionation, targeted constructs, MS substrate ID with in vitro validation, xenografts, and conditional Pten-knockout mice

    PMID:23398121 PMID:23856248

    Open questions at the time
    • Trigger relocalizing active PTK6 to the membrane not fully defined
  17. 2012 Medium

    Defined PTK6 protein stability control through Hsp90/CHIP and HER2-MEK-calpastatin-calpain axes, explaining how PTK6 levels are post-translationally maintained.

    Evidence Co-IP, geldanamycin and proteasome inhibitor experiments, CHIP manipulation; HER2/MEK manipulation with calpain activity and stability assays

    PMID:22849407 PMID:23707532

    Open questions at the time
    • Quantitative balance between proteasomal and calpain pathways in vivo unknown
  18. 2014 Medium

    Showed PTK6 is stabilized under hypoxia with membrane relocalization and motility induction, and degrades the Dok1 tumor suppressor, reinforcing pro-invasive control.

    Evidence Hypoxia/HIF-1α knockdown with ubiquitylation and motility assays; Dok1 Y362 mutagenesis with ubiquitination/proteasome rescue

    PMID:24523872 PMID:25019382

    Open questions at the time
    • Mechanism of hypoxic stabilization not molecularly defined
  19. 2015 High

    Defined PTK6 cell-cycle promotion via p27KIP1 Y88 phosphorylation activating cdk4, and showed cancer mutations activate PTK6 by disrupting autoinhibition.

    Evidence SH3-PXXP interaction screen and in vitro kinase/cdk4 assays for p27; recombinant mutant panel with kinetics for cancer mutations

    PMID:25733683 PMID:25940761

    Open questions at the time
    • Frequency and clinical impact of activating mutations not addressed
  20. 2016 High

    Linked PTK6 to EMT through SNAIL stabilization and E-cadherin suppression, with PTK6 inhibition reducing metastatic colonization by inducing anoikis.

    Evidence siRNA and kinase inhibitor, SNAIL/E-cadherin Western with proteasome rescue, anoikis assay, and in vivo lung colonization

    PMID:27302163

    Open questions at the time
    • Direct PTK6 substrate mediating SNAIL stabilization not pinpointed
  21. 2017 High

    Identified PTEN as a direct PTK6 Y342 phosphatase and a genetic suppressor of PTK6-driven tumorigenesis, and identified Eps8 as a membrane-PTK6 substrate driving proliferation/migration.

    Evidence Phosphatase-dead PTEN constructs, phospho-Y342/Y447 blots, conditional and double-KO mouse prostate models, human tissue; Eps8 phosphosite mutagenesis with functional rescue

    PMID:28214294 PMID:29142193

    Open questions at the time
    • How PTEN loss specifically redirects PTK6 to membranes not fully mechanistic
  22. 2019 High

    Showed PTK6 degrades SMAD4 and is sequestered by PSPC1 in the nucleus, defining a switch governing EMT/metastasis via Wnt/beta-catenin.

    Evidence Co-IP, in vitro phosphorylation with active BRK-Y447F, ubiquitination assays; PSPC1 Y523F mutagenesis with orthotopic HCC model and Wnt reporters

    PMID:31681835 PMID:31844057

    Open questions at the time
    • General applicability of PSPC1 sequestration across tissues untested
  23. 2020 Medium

    Dissociated PTK6 functions from catalysis, showing the SH2 domain drives motility via RhoA/AhR and the SH3 domain drives spheroid formation via p38, with kinase activity dispensable for migration.

    Evidence Domain deletion mutants, RPPA, RhoA/AhR inhibition, and primary breast tumor organoids

    PMID:33172975

    Open questions at the time
    • Mechanism by which the SH2 domain activates RhoA not defined
    • Scaffolding partners mediating kinase-independent functions unidentified
  24. 2018 High

    Provided structural and pharmacological tools, solving PTK6 kinase-domain structures with inhibitors and revealing that growth inhibition often does not track with kinase inhibition.

    Evidence X-ray crystallography of inhibitor complexes and selective inhibitors with 2D/3D growth assays in engineered cells

    PMID:27993680 PMID:29879184

    Open questions at the time
    • Kinase-independent growth-promoting activity not molecularly explained
    • Structure of full-length/autoinhibited enzyme unsolved
  25. 2019 Medium

    Demonstrated repurposed inhibitors (vemurafenib) and JAK2 as a substrate, showing PTK6 activates JAK2/STAT3 to promote cancer stemness and is pharmacologically targetable.

    Evidence STD-NMR/docking and signaling/xenograft assays for vemurafenib; co-IP and kinase-dead mutants with PDX models for JAK2

    PMID:30926642 PMID:34551797

    Open questions at the time
    • Selectivity of repurposed inhibitors for PTK6 in vivo uncertain
  26. 2025 High

    Extended PTK6's RNA-regulatory role to phase separation, showing PTK6 phosphorylates HNRNPH1 to drive condensate formation and NBR1 splicing that activates autophagy and suppresses apoptosis.

    Evidence Co-IP, Y210 phosphorylation, FRAP, NBR1 splicing/autophagy assays, and organoid/CDX models with the inhibitor tilfrinib

    PMID:40103198

    Open questions at the time
    • Generality of LLPS-driven splicing control across PTK6 RNA-binding substrates untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism that determines PTK6's nuclear versus membrane partitioning in cells, and how kinase-independent SH2/SH3 scaffolding functions integrate with catalytic substrate phosphorylation, remain unresolved.
  • No defined cellular signal controlling localization switch
  • Kinase-independent functions lack identified scaffolding mechanism
  • No full-length structure rationalizing autoinhibition and partner engagement

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 5 GO:0005886 plasma membrane 5 GO:0005829 cytosol 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2
Partners
EGFRERBB2IGF1RJAK2PSPC1PTENSAM68STAP2

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 BRK/PTK6 (brk) encodes a novel non-receptor tyrosine kinase with SH3 and SH2 domains that is capable of autophosphorylation on tyrosine residues when expressed in baculovirus and bacterial recombinant systems. Recombinant protein expression (baculovirus and bacterial systems), autophosphorylation assay Oncogene Medium 8036022
1996 Mutation of the catalytic lysine (K219M) abolishes BRK kinase activity and transformation capacity in mammary epithelial cells; mutation of the C-terminal inhibitory tyrosine (Y447F) decreases transforming potential without abolishing kinase activity, indicating Y447 plays a regulatory role distinct from catalysis. Site-directed mutagenesis, transformation assay in human mammary epithelial cells The Journal of biological chemistry Medium 8940083
2000 BRK/Sik associates with the RNA-binding protein Sam68 through its SH3 and SH2 domains; the proline-rich P3 region of Sam68 is required for SH3 binding. BRK/Sik phosphorylates Sam68 in the nucleus (in Sam68-SLM nuclear bodies in HT29 cells and in nucleoplasm of NMuMG cells) and abolishes Sam68's ability to bind RNA and act as a cellular Rev homologue. Co-immunoprecipitation, domain mapping (SH3/SH2 interaction studies), co-transfection, functional RNA-binding assay Molecular and cellular biology High 10913193
2000 BRK associates with and phosphorylates BKS (STAP-2), a novel adaptor protein with PH-like and SH2-like domains; association and phosphorylation are dependent on BRK catalytic activity and on the SH2-like domain of BKS. BKS also recruits an unidentified 100 kDa protein that becomes tyrosine-phosphorylated in the presence of BRK. Yeast two-hybrid screen, co-transfection, co-immunoprecipitation, phosphotyrosine detection Oncogene Medium 10980601
2000 BRK expression in mammary epithelial cells enhances EGF-induced phosphorylation of erbB3, leading to increased recruitment of PI3-kinase to erbB3 and potentiated AKT activation, thereby enhancing mitogenic signaling. Stable transfection of BRK into mammary epithelial cells, Western blotting for phospho-erbB3, PI3K co-immunoprecipitation, AKT activity assay Oncogene Medium 11114724
2002 BRK autophosphorylates within the activation loop (Y342) and at N-terminal sites as shown by mass spectrometry; activation loop autophosphorylation increases kinase activity (Y342A mutant is not activated). The C-terminal Y447 maintains autoinhibition via SH2 domain engagement (Y447F mutation increases activity and SH2 accessibility). The SH3 domain also contributes to autoinhibition, as a proline-rich peptide activates BRK. Baculovirus expression, mass spectrometry, site-directed mutagenesis, in vitro kinase assays with synthetic peptides (Km, kcat measurements), SH2 domain accessibility assay The Journal of biological chemistry High 12121988
2003 Sam68 hyperphosphorylation by activated Sik/BRK in the nucleus inhibits Sam68-mediated cytoplasmic utilization of intron-containing RNA in a dose-dependent manner. The RNA-binding defective Sam68 G178E mutant cannot enhance CTE function, confirming that BRK regulation of Sam68 RNA-binding activity is functionally important. Co-expression of Sik/BRK with Sam68 in 293T cells, RNA analysis, protein expression assays, Sam68 point mutant (G178E) Molecular and cellular biology Medium 12482964
2003 BRK/Sik subcellular localization shifts from nuclear (normal/well-differentiated prostate epithelial cells) to cytoplasmic (poorly differentiated prostate cancer cells), and nuclear BRK is less active in cytoplasmic-localized PC3 cells; altered localization correlates with differentiation state. Immunohistochemistry of 58 prostate biopsy samples, subcellular fractionation, Western blotting of prostate cancer cell lines Oncogene Medium 12833144
2004 BRK SH3 domain mutations that disrupt intramolecular interactions increase BRK kinase activity; the SH3 domain plays the dominant role in substrate recognition. Bifunctional peptides coupling a substrate sequence to an SH3 ligand show significantly lower Km than controls, while SH2-binding substrate peptides show no difference. Site-directed mutagenesis, kinase activity assays in HEK293 cells, synthetic peptide substrate assays (Km measurements), Sam68 phosphorylation comparison Oncogene High 14676834
2004 BRK/Sik phosphorylates SLM-1 and SLM-2 (Sam68-like mammalian proteins) but not hnRNP K; phosphorylation inhibits their RNA-binding abilities and promotes nuclear retention of BRK/Sik. Co-transfection, phosphorylation assays, RNA-binding assay, subcellular localization studies The Journal of biological chemistry Medium 15471878
2004 BRK identifies paxillin as a binding partner and substrate; EGF stimulation activates BRK, which phosphorylates paxillin at Y31 and Y118, promoting Rac1 activation via CrkII, thereby driving cell motility and invasion. BRK translocates to membrane ruffles and colocalizes with paxillin during cell migration. Co-immunoprecipitation, in vitro kinase assay, site-specific phosphorylation mapping, Rac1 activation assay, cell migration and invasion assays, confocal microscopy Molecular and cellular biology High 15572663
2005 BRK associates with IRS-4 via both its SH3 and SH2 domains in resting and IGF-1-stimulated cells; IRS-4 enhances IGF-1-induced BRK tyrosine phosphorylation; endogenous BRK and IRS-4 interact in A431 cells. Co-immunoprecipitation, mass spectrometry identification, domain mapping, EGF/IGF-1 stimulation experiments Oncogene Medium 15870689
2007 The BRK SH3 domain interacts with the SH2-kinase linker region via W44 in the SH3 domain and P175, P177, P179 in the linker; disruption of this interaction by mutagenesis markedly increases PTK6 catalytic activity, demonstrating this intramolecular contact maintains PTK6 in an autoinhibited conformation. Site-directed mutagenesis, surface plasmon resonance, kinase activity assays, 3D structural modeling Biochemical and biophysical research communications High 17822667
2008 BRK is coamplified with ErbB2 in human breast cancers; ErbB2 interacts with BRK and increases its intrinsic kinase activity; BRK expression enhances ErbB2-induced Ras/MAPK signaling and cyclin E/cdk2 activity to promote proliferation; BRK overexpression confers resistance to lapatinib-induced growth inhibition. Co-immunoprecipitation, FISH (gene amplification), 3D acini culture, mouse mammary tumor model (WAP-Brk transgenic), kinase activity assays Proceedings of the National Academy of Sciences of the United States of America High 18719096
2009 BRK phosphorylates PSF (polypyrimidine tract-binding protein-associated splicing factor) at C-terminal tyrosines via an SH3 domain–polyproline interaction; this phosphorylation promotes cytoplasmic relocalization of PSF, impairs its RNA binding, and leads to cell cycle arrest. Proteomic co-immunoprecipitation/mass spectrometry, co-IP, phosphosite mapping, subcellular fractionation, RNA-binding assay, cell cycle analysis Cellular signalling High 19439179
2009 Membrane-targeted PTK6 (Myr-PTK6) promotes proliferation, cell survival, migration, and anchorage-independent colony formation, whereas nuclear-targeted PTK6 (NLS-PTK6) impairs these functions; the two localizations produce distinct cellular phosphoproteome profiles. Targeted localization constructs (myristoylation signal vs. NLS), proliferation/survival/migration/colony formation assays, phosphoprotein profiling in HEK293 cells Journal of biochemistry Medium 19304789
2009 STAP-2 is phosphorylated at Y250 by BRK; the STAP-2 Y250F mutant attenuates BRK-mediated STAT3 activation; siRNA knockdown of STAP-2 decreases BRK-mediated STAT3 activation, establishing STAP-2 as a required intermediary in BRK→STAT3 signaling. Site-directed mutagenesis (Y250F), anti-phospho-STAP-2 Y250 antibody, siRNA knockdown, STAT3 activation assays Biochemical and biophysical research communications Medium 19393627
2009 PTK6 directly phosphorylates beta-catenin predominantly at Y64 (also Y142, Y331/333); PTK6 associates with nuclear and cytoplasmic beta-catenin and inhibits beta-catenin/TCF-mediated transcription. Nuclear-targeted PTK6 negatively regulates beta-catenin/TCF transcription and increases TCF4 and TLE/Groucho co-repressor levels, while membrane-targeted PTK6 enhances beta-catenin/TCF transcription. In vitro kinase assay, phosphosite mapping, co-immunoprecipitation, luciferase reporter assay, siRNA knockdown, Ptk6-null BAT-GAL reporter mice Journal of cell science High 20026641
2010 PTK6 forms a complex with IGF-1R and IRS-1 adaptor protein, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. siRNA screen, reverse-phase protein arrays, co-immunoprecipitation PloS one Medium 20668531
2010 STAP-2 interacts with both BRK and STAT3; STAP-2 PH domain is required for BRK–STAP-2 binding, BRK kinase activation, and STAT3 tyrosine phosphorylation/activation; a STAP-2 PH-Brk fusion protein exhibits robust kinase activity and enhanced STAT3 activation. Co-immunoprecipitation, domain deletion mapping, siRNA knockdown, STAT3 activation assays, fusion protein kinase activity The Journal of biological chemistry Medium 20929863
2010 PTK6 phosphorylates ARAP1 at Y231 in an EGF/EGFR-dependent manner via the PTK6 SH2 domain (R105 residue); phosphorylated ARAP1 inhibits EGFR down-regulation, thereby sustaining EGFR signaling. PTK6 silencing in breast cancer cells decreases EGFR levels. Co-immunoprecipitation, MALDI-TOF mass spectrometry identification, site-directed mutagenesis (Y231F, R105A), EGFR degradation assay The Journal of biological chemistry High 20554524
2011 STAP-2 mediates BRK-induced STAT5 phosphorylation and activation in T47D breast cancer cells; the STAP-2 PH domain participates in BRK-mediated STAT5 phosphorylation; knockdown of STAP-2 reduces proliferation as strongly as BRK or STAT5b knockdown. Co-transfection, STAT5 transcriptional reporter, siRNA knockdown, proliferation assays Cancer science Medium 21205088
2011 ALT-PTK6, an alternatively spliced form lacking exon 2, associates with Sam68 and beta-catenin via its SH3 domain (demonstrated by GST pull-down); coexpression of ALT-PTK6 with full-length PTK6 suppresses PTK6 kinase activity, reduces PTK6 association with phosphotyrosine proteins, and enhances PTK6-mediated inhibition of beta-catenin/TCF transcription by promoting nuclear PTK6 function. RT-PCR, GST pull-down, co-immunoprecipitation, luciferase reporter assay, inducible expression system, proliferation/colony assays PloS one Medium 21479203
2011 BRK mediates p38 MAPK phosphorylation downstream of EGF signaling in mammary epithelial cells; BRK knockdown blocks EGF-stimulated p38 signaling; BRK overexpression in mammary gland causes delayed involution associated with activated p38 MAPK. WAP-Brk transgenic mouse model, siRNA knockdown, Western blotting, IHC Breast cancer research : BCR Medium 21923922
2012 BRK interacts with EGFR, inhibits ligand-induced EGFR degradation by uncoupling activated EGFR from c-Cbl-mediated ubiquitination, and directly phosphorylates EGFR Y845 in the kinase domain to potentiate EGFR kinase activity. Co-immunoprecipitation, ubiquitination assay, in vitro kinase assay (phospho-Y845), EGFR degradation assay, siRNA knockdown Oncogene High 22231447
2012 BRK is a critical downstream effector of Met/HGF signaling and is required for HGF-induced cell migration in breast cancer cells. siRNA knockdown of BRK with HGF stimulation, cell migration assay Hormones & cancer Low 22124844
2013 PTP1B dephosphorylates BRK/PTK6 directly and also dephosphorylates IGF-1R β-subunit; BRK physically interacts with IGF-1R β-subunit. Restoration of PTP1B in ovarian cancer cells attenuates PTK6 and IGF-1R signaling, activating BAD to induce apoptosis. Stable PTP1B re-expression, co-immunoprecipitation (PTK6-IGF-1R), phosphorylation assays, apoptosis assays The Journal of biological chemistry Medium 23814047
2013 Active PTK6 in prostate cancer cells localizes to the plasma membrane; membrane-targeted active PTK6 promotes EMT partly by enhancing AKT activation and stimulates cancer cell migration and metastasis in xenograft models; in PTEN-null mouse prostate, endogenous active PTK6 localizes to membranes with decreased E-cadherin. Subcellular fractionation, targeted PTK6 constructs (membrane/cytoplasm), siRNA knockdown, AKT phosphorylation assays, xenograft mouse model, conditional Pten-knockout mouse Cancer research High 23856248
2013 AKT, p130CAS, and FAK are identified as PTK6 substrates by mass spectrometry and validated by in vitro phosphorylation assays; these substrates promote cell proliferation, migration, and anoikis resistance downstream of cytoplasmic/membrane-localized PTK6 in prostate cancer. Mass spectrometry substrate identification, in vitro kinase assay validation, siRNA knockdown, targeted PTK6 expression constructs European journal of clinical investigation Medium 23398121
2013 PTK6 phosphorylates and degrades c-Cbl at Y700, Y731, and Y774 in the C-terminal domain; phosphorylated c-Cbl undergoes auto-ubiquitination and proteasomal degradation, thereby reducing c-Cbl-mediated ubiquitination of substrates. Co-immunoprecipitation, site-directed mutagenesis of c-Cbl phosphosites, ubiquitination assay, proteasome inhibitor experiments Biochemical and biophysical research communications Medium 23352614
2014 BRK interacts with and phosphorylates Dok1 specifically at Y362; this phosphorylation leads to ubiquitin-proteasome-mediated Dok1 degradation, thereby removing a tumor suppressor and promoting cell proliferation and migration. Co-immunoprecipitation, in vitro kinase assay, phosphosite mapping (Y362), ubiquitination assay, proteasome inhibitor rescue PloS one Medium 24523872
2014 BRK phosphorylates KAP3A (kinesin-associated protein 3A) at C-terminal tyrosine residues in vivo; BRK-mediated phosphorylation induces delocalization of KAP3A from punctate nuclear localization to diffuse nucleo-cytoplasmic pattern; KAP3A knockdown suppresses BRK-induced cell migration. High-density protein filter array kinase screen, in vivo phosphorylation assay, co-immunoprecipitation, subcellular localization imaging, siRNA knockdown, migration assay Cellular signalling Medium 18077133
2015 BRK phosphorylates p27KIP1 at Y88 via an SH3-PXXP interaction; pY88-p27 activates cyclin D-cdk4 activity. An alternatively spliced form of BRK (Alt Brk) containing only the SH3 domain blocks pY88 and acts as an endogenous cdk4 inhibitor. SH3-PXXP interaction screen, in vitro kinase assay, pY88 phosphorylation assay in breast cancer cells, modulation of BRK levels in cells, cdk4 activity assay Molecular and cellular biology Medium 25733683
2015 Cancer-associated somatic mutations in BRK SH3 (L16F), SH2 (R131L), and C-terminal tail (P450L) domains activate BRK by disrupting intramolecular autoinhibitory interactions; two other mutations eliminate enzymatic activity; mutations differentially affect substrate recognition and phosphorylation. Recombinant protein expression, in vitro kinase assays, mutagenesis panel, substrate peptide assays Biochemistry High 25940761
2016 PTK6 downregulation restores E-cadherin levels via proteasome-dependent degradation of the E-cadherin repressor SNAIL; kinase-active PTK6 suppresses E-cadherin expression and promotes EMT markers; PTK6 inhibition impairs metastatic lung colonization in vivo through anoikis induction. siRNA knockdown, PTK6 kinase inhibitor, E-cadherin/SNAIL Western blotting, proteasome inhibitor rescue, anoikis assay, in vivo lung colonization assay Cancer research High 27302163
2016 PTK6 interacts with JAK2 and phosphorylates it to activate JAK2/STAT3 signaling, thereby promoting cancer cell stemness in colorectal cancer. Pharmacological inhibition of PTK6 with XMU-MP-2 reduces stemness and chemosensitivity in vivo. Co-immunoprecipitation (PTK6-JAK2), FLAG-tagged PTK6 mutant constructs (kinase-dead, inhibition-defective), STAT3 activation assays, in vivo xenograft/PDX models Journal of experimental & clinical cancer research : CR Medium 34551797
2017 PTEN protein phosphatase activity directly dephosphorylates PTK6 at activation loop Y342 (but not autoinhibitory Y447), inhibiting PTK6 activity with efficiency similar to PTP1B. In PTEN-null prostate cancer, conditional Pten disruption increases PTK6 Y342 phosphorylation and tumorigenesis; Ptk6 disruption impairs PTEN-loss-induced tumorigenesis. PTEN mutant constructs (phosphatase-dead), phospho-Y342 and Y447 Western blotting, PTEN knockdown/re-expression, conditional Pten-knockout mouse prostate model, Ptk6/Pten double-KO mice, human prostate tumor tissue microarrays Nature communications High 29142193
2017 Plasma membrane-localized PTK6 phosphorylates Eps8 at Y497, Y524, and Y534; Eps8 3YF phosphorylation-defective mutant reverts PTK6-mediated increases in proliferation, migration, ERK phosphorylation, and FAK phosphorylation; EGF-induced Eps8 phosphorylation in T-47D cells depends on endogenous PTK6. Proteomics screen with Myr-PTK6, site-directed mutagenesis (Eps8 3YF), kinase assays, siRNA knockdown in breast cancer cells, proliferation/migration/adhesion assays Journal of cellular biochemistry Medium 28214294
2018 Crystal structures of PTK6 kinase domain were solved in complex with Dasatinib (2.24 Å) and a novel IPA compound (1.70 Å); both structures are in DFG-in, αC-helix-out conformation with inhibitors at the ATP-binding pocket; Dasatinib occupies an additional pocket near the gatekeeper explaining its higher potency. X-ray crystallography (co-crystal structures of PTK6-KD with inhibitors), structure determination and refinement Biochemical and biophysical research communications High 27993680
2018 Crystal structure of apo-PTK6 and inhibitor-bound PTK6 complexes were determined; PTK6 kinase inhibitors moderately suppress tumor cell growth in 2D/3D culture but growth inhibition does not correlate with PTK6 kinase activity inhibition or PTK6 protein levels (>500-fold shift between kinase IC50 and growth inhibition IC50 in PTK6-overexpressing cells), indicating PTK6 kinase activity is not the primary driver of tumor growth. Crystal structure determination (apo and inhibitor-bound), selective PTK6 inhibitors with kinase assays, 2D/3D cell growth assays, PTK6 overexpression in engineered breast tumor cells PloS one Medium 29879184
2019 BRK phosphorylates SMAD4 leading to its recognition by the ubiquitin-proteasome system and accelerated degradation; activated BRK (Y447F mutant) mediates SMAD4 degradation associated with repression of tumor suppressor FRK and increased expression of SNAIL and SLUG. BRK competitively binds SMAD4. Co-immunoprecipitation, in vitro phosphorylation assay with constitutively active BRK-Y447F, ubiquitination assay, proteasome inhibitor rescue, knockdown experiments Science advances Medium 31681835
2019 PSPC1 is a nuclear substrate of PTK6; PSPC1 sequesters PTK6 in the nucleus and inhibits its metastasis-promoting function. PSPC1 upregulation or PSPC1-Y523F mutation promotes cytoplasmic translocation of active PTK6 and nuclear translocation of beta-catenin, driving EMT and metastasis via augmented Wnt3a autocrine signaling. PSPC1-CT131 acts as a dual inhibitor of PSPC1 and PTK6. Co-immunoprecipitation (PSPC1-PTK6, PSPC1-beta-catenin), site-directed mutagenesis (Y523F), subcellular localization imaging, HCC orthotopic mouse model, beta-catenin/Wnt reporter assays Nature communications High 31844057
2020 The PTK6 SH2 domain (not the kinase domain) mediates cell motility in TNBC via activation of RhoA and aryl hydrocarbon receptor (AhR) signaling pathways; the SH3 domain contributes to spheroid formation via p38 MAPK. Kinase activity is dispensable for cell migration but contributes to anchorage-independent colony formation. In-frame domain deletion mutants (SH2-del, SH3-del, kinase-dead), reverse-phase protein arrays, RhoA/AhR inhibition, primary breast tumor organoids Molecular cancer research : MCR Medium 33172975
2012 Hsp90 interacts with the PTK6 tyrosine kinase catalytic domain (interaction is independent of catalytic activity) and protects PTK6 from proteasomal degradation. Geldanamycin (Hsp90 inhibitor) decreases PTK6 protein via proteasome-dependent degradation and increases PTK6 interaction with the E3 ligase CHIP; CHIP overexpression promotes PTK6 proteasomal degradation. Co-immunoprecipitation, geldanamycin treatment, proteasome inhibitor rescue, CHIP overexpression, siRNA knockdown of CHIP The Biochemical journal Medium 22849407
2013 HER2 stabilizes BRK protein by upregulating calpastatin (an endogenous calpain inhibitor) via MEK signaling, thereby inhibiting calpain-1-mediated proteolytic degradation of BRK. HER2 knockdown downregulates calpastatin, increasing calpain-1 activity and BRK degradation. HER2 overexpression/siRNA knockdown, BRK stability assays, calpain activity assay, calpastatin expression analysis, MEK inhibition, constitutively active MEK rescue Cellular signalling Medium 23707532
2014 Under hypoxic conditions, PTK6 is rapidly stabilized (in a HIF-1α-independent manner) associated with decreased ubiquitylation; c-Cbl is identified as a putative PTK6 E3 ubiquitin ligase in normoxia. Hypoxia-induced PTK6 stabilization and membrane relocalization is associated with increased cell motility and invasion. Hypoxia treatment, HIF-1α knockdown, ubiquitylation assay, c-Cbl co-immunoprecipitation, subcellular fractionation, cell motility/invasion assays Cancer biology & therapy Medium 25019382
2019 Vemurafenib (PLX4032/PLX4720) binds in the active site of PTK6 as demonstrated by saturation transfer difference NMR and molecular docking; vemurafenib inhibits PTK6-mediated signaling through FAK, EGFR, and ERK1/2 and blocks PTK6-dependent cell growth, migration, and invasion in prostate cancer models. Saturation transfer difference NMR, molecular docking, kinase assays, signaling Western blots, xenograft model Molecular cancer therapeutics High 30926642
2025 PTK6 physically interacts with HNRNPH1 and phosphorylates it at Y210, promoting HNRNPH1 liquid-liquid phase separation (LLPS) and formation of biomolecular condensates; HNRNPH1 LLPS triggers splicing switching of NBR1 exon 10 inclusion, activating autophagy and suppressing apoptosis in colorectal cancer. Co-immunoprecipitation (PTK6-HNRNPH1), Y210 phosphorylation assay, FRAP (LLPS validation), NBR1 splicing assay, autophagy assays, patient-derived organoid and CDX models with PTK6 inhibitor tilfrinib Autophagy High 40103198

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours. Oncogene 148 8036022
1997 BRK tyrosine kinase expression in a high proportion of human breast carcinomas. Oncogene 136 9266966
2000 Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability. Molecular and cellular biology 135 10913193
2004 Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin. Molecular and cellular biology 132 15572663
2003 Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Oncogene 114 12833144
1996 Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor. The Journal of biological chemistry 104 8940083
1999 BRK/Sik expression in the gastrointestinal tract and in colon tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 98 10430081
2000 Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation. Oncogene 95 11114724
2008 Brk is coamplified with ErbB2 to promote proliferation in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 92 18719096
2003 Sam68 enhances the cytoplasmic utilization of intron-containing RNA and is functionally regulated by the nuclear kinase Sik/BRK. Molecular and cellular biology 92 12482964
2003 Brk, Srm, Frk, and Src42A form a distinct family of intracellular Src-like tyrosine kinases. Oncology research 92 12725532
2010 Building a better understanding of the intracellular tyrosine kinase PTK6 - BRK by BRK. Biochimica et biophysica acta 86 20193745
2002 Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition. The Journal of biological chemistry 80 12121988
2012 Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma. Gastroenterology 74 22705009
2004 The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2. The Journal of biological chemistry 72 15471878
2000 A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK. Oncogene 71 10980601
2010 PTK6 regulates IGF-1-induced anchorage-independent survival. PloS one 66 20668531
2003 Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation. Oncogene 65 12902983
2017 PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer. Nature communications 64 29142193
2006 The BRK tyrosine kinase is expressed in high-grade serous carcinoma of the ovary. Cancer biology & therapy 63 16855388
2010 Brk/PTK6 signaling in normal and cancer cell models. Current opinion in pharmacology 57 20832360
2016 PTK6 Inhibition Suppresses Metastases of Triple-Negative Breast Cancer via SNAIL-Dependent E-Cadherin Regulation. Cancer research 56 27302163
2009 BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest. Cellular signalling 55 19439179
2005 Simultaneous over-expression of the Her2/neu and PTK6 tyrosine kinases in archival invasive ductal breast carcinomas. The Journal of pathology 54 15685689
2009 Identification of beta-catenin as a target of the intracellular tyrosine kinase PTK6. Journal of cell science 52 20026641
2005 Interaction between Brk kinase and insulin receptor substrate-4. Oncogene 51 15870689
2016 Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. Cancer research 49 26825173
2013 Protein-tyrosine phosphatase 1B antagonized signaling by insulin-like growth factor-1 receptor and kinase BRK/PTK6 in ovarian cancer cells. The Journal of biological chemistry 49 23814047
2013 Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression. Cancer research 48 23928995
2012 Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR. Oncogene 48 22231447
2014 RSK promotes prostate cancer progression in bone through ING3, CKAP2, and PTK6-mediated cell survival. Molecular cancer research : MCR 46 25189355
2004 Role of the Brk SH3 domain in substrate recognition. Oncogene 45 14676834
2009 STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation. Biochemical and biophysical research communications 44 19393627
2013 PTK6 activation at the membrane regulates epithelial-mesenchymal transition in prostate cancer. Cancer research 43 23856248
2009 Brk protects breast cancer cells from autophagic cell death induced by loss of anchorage. The American journal of pathology 43 19661439
2016 TNFα/IFNγ Mediated Intestinal Epithelial Barrier Dysfunction Is Attenuated by MicroRNA-93 Downregulation of PTK6 in Mouse Colonic Epithelial Cells. PloS one 41 27119373
2012 Mechanisms of HGF/Met signaling to Brk and Sam68 in breast cancer progression. Hormones & cancer 41 22124844
2010 Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. The Journal of biological chemistry 41 20929863
1997 Characterisation and chromosome mapping of the human non receptor tyrosine kinase gene, brk. Oncogene 41 9333026
2019 PSPC1-interchanged interactions with PTK6 and β-catenin synergize oncogenic subcellular translocations and tumor progression. Nature communications 40 31844057
2015 Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4. Molecular and cellular biology 40 25733683
2004 Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium. Oral oncology 40 15509496
2015 PTK6 inhibition promotes apoptosis of Lapatinib-resistant Her2(+) breast cancer cells by inducing Bim. Breast cancer research : BCR 39 26084280
2013 Context-specific protein tyrosine kinase 6 (PTK6) signalling in prostate cancer. European journal of clinical investigation 38 23398121
2021 Pharmacological targeting PTK6 inhibits the JAK2/STAT3 sustained stemness and reverses chemoresistance of colorectal cancer. Journal of experimental & clinical cancer research : CR 36 34551797
2014 PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling. PloS one 36 24788754
2007 Breast tumor kinase BRK requires kinesin-2 subunit KAP3A in modulation of cell migration. Cellular signalling 36 18077133
2006 Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes. The American journal of pathology 35 16651629
2004 The Brk protein tyrosine kinase as a therapeutic target in cancer: opportunities and challenges. Anti-cancer drugs 35 15075665
1998 Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase. Molecules and cells 34 9749526
2015 Tracing the footprints of the breast cancer oncogene BRK - Past till present. Biochimica et biophysica acta 33 25999240
2009 Oncogenic functions of PTK6 are enhanced by its targeting to plasma membrane but abolished by its targeting to nucleus. Journal of biochemistry 33 19304789
2011 Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells. Cancer science 31 21205088
2010 PTK6 inhibits down-regulation of EGF receptor through phosphorylation of ARAP1. The Journal of biological chemistry 31 20554524
2007 Solution structure of the BRK domains from CHD7. Journal of molecular biology 31 17603073
2019 MicroRNA-214 targets PTK6 to inhibit tumorigenic potential and increase drug sensitivity of prostate cancer cells. Scientific reports 30 31278310
2013 Brk regulates wing disc growth in part via repression of Myc expression. EMBO reports 30 23337628
2005 The intracellular tyrosine kinase Brk sensitizes non-transformed cells to inducers of apoptosis. Cell cycle (Georgetown, Tex.) 30 16082217
2017 PTK6 regulates growth and survival of endocrine therapy-resistant ER+ breast cancer cells. NPJ breast cancer 29 29167821
2013 Brk/PTK6 cooperates with HER2 and Src in regulating breast cancer cell survival and epithelial-to-mesenchymal transition. Cancer biology & therapy 29 23291984
2011 Impact of protein tyrosine kinase 6 (PTK6) on human epidermal growth factor receptor (HER) signalling in breast cancer. Molecular bioSystems 29 21380407
2011 Discovery of novel imidazo[1,2-a]pyrazin-8-amines as Brk/PTK6 inhibitors. Bioorganic & medicinal chemistry letters 28 21855335
2011 Mammary gland specific expression of Brk/PTK6 promotes delayed involution and tumor formation associated with activation of p38 MAPK. Breast cancer research : BCR 28 21923922
2015 Generation of high-titre virus stocks using BrK.219, a B-cell line infected stably with recombinant Kaposi's sarcoma-associated herpesvirus. Journal of virological methods 27 25736227
2012 Hsp90 rescues PTK6 from proteasomal degradation in breast cancer cells. The Biochemical journal 27 22849407
2020 Strategic Developments & Future Perspective on Gene Therapy for Breast Cancer: Role of mTOR and Brk/ PTK6 as Molecular Targets. Current gene therapy 26 32807051
2016 Targeting BRK-Positive Breast Cancers with Small-Molecule Kinase Inhibitors. Cancer research 26 27758886
2014 Discovery, optimization, and pharmacophore modeling of oleanolic acid and analogues as breast cancer cell migration and invasion inhibitors through targeting Brk/Paxillin/Rac1 axis. Chemical biology & drug design 26 24954090
2014 PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors. Oncotarget 26 25153721
2010 In situ quantification of HER2-protein tyrosine kinase 6 (PTK6) protein-protein complexes in paraffin sections from breast cancer tissues. British journal of cancer 26 20700126
2016 Kinase-Dependent and -Independent Roles for PTK6 in Colon Cancer. Molecular cancer research : MCR 25 26983689
2013 Effects of simultaneous knockdown of HER2 and PTK6 on malignancy and tumor progression in human breast cancer cells. Molecular cancer research : MCR 23 23364537
2008 Conditionally immortalized colonic epithelial cell line from a Ptk6 null mouse that polarizes and differentiates in vitro. Journal of gastroenterology and hepatology 23 18205771
2014 Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity. Cancer letters 22 25193464
2023 PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation. Cell death & disease 21 36690663
2014 Marine natural products-inspired phenylmethylene hydantoins with potent in vitro and in vivo antitumor activities via suppression of Brk and FAK signaling. Organic & biomolecular chemistry 21 24927150
2011 The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of β-catenin. PloS one 21 21479203
2021 Putting the BRK on breast cancer: From molecular target to therapeutics. Theranostics 20 33391524
2020 Breast Tumor Kinase (Brk/PTK6) Mediates Advanced Cancer Phenotypes via SH2-Domain Dependent Activation of RhoA and Aryl Hydrocarbon Receptor (AhR) Signaling. Molecular cancer research : MCR 20 33172975
2018 Small molecule inhibitors reveal PTK6 kinase is not an oncogenic driver in breast cancers. PloS one 20 29879184
2015 PTK6 Potentiates Gemcitabine-Induced Apoptosis by Prolonging S-phase and Enhancing DNA Damage in Pancreatic Cancer. Molecular cancer research : MCR 20 26013168
2018 Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF-driven Signaling Axis. Molecular cancer research : MCR 19 29991529
2017 PTK6 Localized at the Plasma Membrane Promotes Cell Proliferation and MigratiOn Through Phosphorylation of Eps8. Journal of cellular biochemistry 19 28214294
1990 Transformation of primary BRK cells by human papillomavirus type 16 and EJ-ras is increased by overexpression of the viral E2 protein. The Journal of general virology 19 2154535
2014 Discovery of 4-anilino α-carbolines as novel Brk inhibitors. Bioorganic & medicinal chemistry letters 18 24650640
2020 Structure of the BRK domain of the SWI/SNF chromatin remodeling complex subunit BRG1 reveals a potential role in protein-protein interactions. Protein science : a publication of the Protein Society 17 31909846
2016 Co-crystal structures of PTK6: With Dasatinib at 2.24 Å, with novel imidazo[1,2-a]pyrazin-8-amine derivative inhibitor at 1.70 Å resolution. Biochemical and biophysical research communications 17 27993680
2014 BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration. PloS one 17 24523872
2014 The marine-derived sipholenol A-4-O-3',4'-dichlorobenzoate inhibits breast cancer growth and motility in vitro and in vivo through the suppression of Brk and FAK signaling. Marine drugs 17 24736807
2014 HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion. Cancer biology & therapy 17 25019382
2025 PTK6 drives HNRNPH1 phase separation to activate autophagy and suppress apoptosis in colorectal cancer. Autophagy 16 40103198
2011 The NAB-Brk signal bifurcates at JNK to independently induce apoptosis and compensatory proliferation. The Journal of biological chemistry 16 21385866
2011 Detection of Brk expression in non-small cell lung cancer: clinicopathological relevance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 21603980
2007 Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6. Biochemical and biophysical research communications 15 17822667
2019 BRK phosphorylates SMAD4 for proteasomal degradation and inhibits tumor suppressor FRK to control SNAIL, SLUG, and metastatic potential. Science advances 14 31681835
2013 HER2 regulates Brk/PTK6 stability via upregulating calpastatin, an inhibitor of calpain. Cellular signalling 14 23707532
2019 Vemurafenib Inhibits Active PTK6 in PTEN-null Prostate Tumor Cells. Molecular cancer therapeutics 13 30926642
2015 Cancer-Associated Mutations in Breast Tumor Kinase/PTK6 Differentially Affect Enzyme Activity and Substrate Recognition. Biochemistry 13 25940761
2014 Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo. Molecular oncology 12 25241146
2013 PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation. Biochemical and biophysical research communications 12 23352614

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