Property Summary

NCBI Gene PubMed Count 92
PubMed Score 167.06
PubTator Score 107.85

Knowledge Summary

Patent (16,143)


  Differential Expression (13)

Disease log2 FC p
osteosarcoma 1.422 1.9e-06
intraductal papillary-mucinous adenoma (... 2.100 9.5e-04
intraductal papillary-mucinous carcinoma... 2.200 1.6e-03
intraductal papillary-mucinous neoplasm ... 2.800 2.0e-03
pancreatic cancer 2.500 3.1e-08
interstitial cystitis -2.000 1.1e-04
cystic fibrosis -1.500 1.5e-04
lung adenocarcinoma 1.600 2.4e-09
nasopharyngeal carcinoma -1.100 1.8e-06
spina bifida -2.768 4.1e-02
ductal carcinoma in situ 1.500 6.6e-03
invasive ductal carcinoma 1.200 3.0e-03
ovarian cancer 1.400 4.2e-09

MLP Assay (1)

AID Type Active / Inconclusive / Inactive Description
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448

Gene RIF (65)

26825173 PELP1 interacted with GR to activate Brk expression.
26013168 PTK6 prolongs S-phase and increases the ability of gemcitabine to cause DNA damage in vitro and in vivo
25940761 Activating mutations in BRK in breast cancer may disrupt intramolecular interactions that normally maintain BRK in an autoinhibited conformation.
25897081 PTP1B inhibited BRK by dephosphorylating Tyr-342, but activated SRC by antagonizing PAG-dependent inhibition by CSK.
25838168 Establishment of cross talk between PTK6 and CagA by functional studies may further elucidate the underlying biology of H. pylori-mediated gastric cancer
25770659 BRK expression in a majority of CC can interact with RTK, augmenting growth and interfering with proliferation inhibitors (SAM68). Therapeutically targeting BRK function (in addition to RTK) should be of benefit for CC treatment.
25748447 overexpression or knockdown of PTK6 or ERK1/2 effectively removed the inhibition of S1P-induced migration by miR-17.
25733683 This study shows that Brk phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.
25377660 Down-regulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma.
25241146 Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression
25153721 PTK6 is expressed in the normal human mammary gland, but does not appear to be active and may have kinase-independent functions that are distinct from its cancer promoting activities at the membrane.
25019382 Hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential.
24788754 PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.
24523872 BRK has a role in targeting Dok1 for ubiquitin-mediated proteasomal degradation and in promoting cell proliferation and migration
23928995 High PTK6 expression is associated with hypoxia-associated breast cancer progression.
23856248 Highly active PTK6 promoted epithelial-mesenchymal transition by enhancing activation of AKT, thereby stimulating cancer cell migration and metastases in xenograft models of prostate cancer.
23814047 an important role for PTP1B as a negative regulator of BRK and IGF-1Rbeta signaling in ovarian cancer cells.
23758975 Protein tyrosine kinase 6 may have a role in poor prognosis and metastasis of nasopharyngeal carcinoma
23707532 Degradation of Brk involved a calpain-1-mediated proteolytic pathway and indicated an inverse relationship between the level of HER2 expression and calpain-1 activity.
23497344 present findings indicated that cytoplasmic PTK6 expression is a potential prognostic factor for survival in LSCC patients. High expression of PTK6 was associated with favorable OS and DFS in LSCC patients
23352614 These results provide evidence for a novel mechanism demonstrating the oncogenic potential of PTK6 through degradation of c-Cbl, which is an E3 ligase important in down-regulation of oncoproteins.
23291984 Brk/PTK6 cooperates with HER2 and Src in regulating breast cancer cell survival and epithelial-to-mesenchymal transition.
23027128 Protein tyrosine kinase 6 protects cells from anoikis by directly phosphorylating focal adhesion kinase and activating AKT.
22989419 Knockdown of PTK6 enhances apoptosis in HCT116 cells with wild-type p53.
22849407 results demonstrate that Hsp90 plays an essential role in regulating PTK6 stability and suggest that Hsp90 inhibitors may be useful as therapeutic drugs for PTK6-positive cancers, including breast cancer
22705009 PTK6 was identified as a transcript that is down-regulated in human esophageal squamous cell carcinoma via epigenetic modification at the PTK6 locus.
22547065 Suppressor of cytokine signaling 3 inhibits breast tumor kinase activation of STAT3.
22231447 breast tumor kinase (Brk)/protein-tyrosine kinase 6 (PTK6), a nonreceptor protein-tyrosine kinase highly expressed in most human breast tumors, interacted with EGFR and sustained ligand-induced EGFR signaling.
22084245 a novel function for PTK6 at the plasma membrane
21923922 Brk expression in human breast tumors may contribute to progression by inducing p38-driven pro-survival signaling pathways.
21603980 present findings indicate an increase of cytoplasmic Brk expression in non-small cell lung cancer
21479203 Alternative transcript-PTK6 is able to negatively regulate growth and modulate PTK6 activity, protein-protein associations and/or subcellular localization.
21380407 Data suggest that since PTK6 plays an important role in HER receptor signal transduction, its down-regulation might be suitable for future therapy approaches in breast cancer.
21240512 show that as primary human keratinocytes are induced to differentiate in vitro, Brk levels decrease
20929863 Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.
20687930 Results identified Brk and ERK5 as important downstream effectors of Met signaling to cell migration.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20606012 AKT is a direct substrate of PTK6 and AKT tyrosine residues 315 and 326 are phosphorylated by PTK6.
20554524 PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.
20162673 Brk antagonizes the transcriptional activity of the transcription factor FoxO family of proteins by inhibiting its nuclear localization. As a result, the cell cycle inhibitor p27, a FoxO target gene, is down-regulated.
20026641 PTK6 associates with nuclear and cytoplasmic beta-catenin and inhibits beta-catenin- and T-cell factor (TCF)-mediated transcription.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19661439 Brk enhances breast carcinoma cell survival in suspension, suggesting a role for Brk in supporting breast cancer cell dissemination
19621240 PTK6 overexpression is not essentially attributed to gene amplification, and the PTK6 protein expression-but not gene status-is of prognostic value in breast carcinomas. PTK6 protein overexpression may result from polysomy 20 in a minority of the tumors.
19439179 The breast tumor kinase SH3-domain interacted with N-terminal polyproline rich motifs of PTB-associated splicing factor and the PTB-associated splicing factor C-terminal tyrosines are the site of tyrosine phosphorylation by breast tumor kinase.
19401189 the structural basis of the SH3-Linker interaction that results in auto-inhibition of PTK6 was reported.
19393627 STAP-2 is phosphorylated at Tyr250 by Brk, and plays an important role in Brk-mediated STAT3 activation.
19304789 PTK6 performs contrasting roles in tumorigenicity depending on its intracellular localization, displaying increased oncogenic abilities when targeted to the plasma membrane and decreased oncogenicity when targeted to the nucleus.
18829532 A previously unknown function of Brk in regulating both RhoA and Ras by phosphorylating p190 and a crucial role of this Brk-elicited signaling pathway in promoting breast malignancy.
18781181 PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of >or=240 months was directly associated with the protein expression level of PTK6
18719096 PTK6 is coamplified and coexpressed with ERBB2 in human breast cancers. ERBB2 interacts with PTK6 and increases its intrinsic kinase activity
18077133 These findings therefore reveal new substrates of BRK and define KAP3A as a physiological substrate of BRK during cell migration.
17997837 Brk can directly phosphorylate STAT5b on Y699. Subsequently, this Brk-mediated STAT5b phosphorylation leads to STAT5b transcriptional activity, and this activity is further increased by kinase active c-Src.
16651629 Our results indicate that Brk may play a key role in lymphomagenesis, hence identifying the kinase as a potential therapeutic target in lymphomas.
16568091 Activates Stat3.
16179349 Sam68 suppresses BRK-induced cell proliferation, and regulates intranuclear localization and cell cycle progression
15961400 the interaction between SH2-kinase linker and kinase domain is essential for the catalytic activity of PTK6
15870689 endogenous Brk and IRS-4 interact in A431 human epidermoid carcinoma cells
15572663 BRK activates rac1 and promotes cell migration and invasion by phosphorylating paxillin.
15539407 in breast cancer cells breast tumor kinase (Brk) behaves similarly to a constitutively active Brk mutant (YF-Brk) and associates with tyrosine-phosphorylated proteins in deregulated signaling complexes
15056653 Results describe the solution structure and backbone dynamics of the human protein-tyrosine kinase-6 Src homology 2 (SH2) domain using multidimensional NMR spectroscopy.
14676834 Study suggests that SH3 interactions will govern phosphorylation of many substrates by BRK.
12833144 BRK plays a role in differentiation of prostate epithelial cells
12725532 The tyrosine kinases Brk/PTK6/Sik, Srm, Frk/Rak/Gtk/Iyk/Bsk, and Src42A/Dsrc41 have a low degree of sequence homology to other known kinases. The exon structure of these kinases, called the Brk family, is highly conserved and distinct.
12482964 the effect of Sam68 was inhibited in a dose-dependent manner by coexpression of an activated form of the nuclear kinase Sik/BRK that hyperphosphorylated Sam68

AA Sequence

LTCWCRDPEQRPCFKALRERLSSFTSYENPT                                           421 - 451

Text Mined References (101)

PMID Year Title
27480927 2016 Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 ? resolution.
26825173 2016 Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer.
26751287 2016 The LINK-A lncRNA activates normoxic HIF1? signalling in triple-negative breast cancer.
26013168 2015 PTK6 Potentiates Gemcitabine-Induced Apoptosis by Prolonging S-phase and Enhancing DNA Damage in Pancreatic Cancer.
25940761 2015 Cancer-Associated Mutations in Breast Tumor Kinase/PTK6 Differentially Affect Enzyme Activity and Substrate Recognition.
25897081 2015 Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase.
25838168 2015 Signature of positive selection of PTK6 gene in East Asian populations: a cross talk for Helicobacter pylori invasion and gastric cancer endemicity.
25770659 2015 Breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6) activity in normal and neoplastic biliary epithelia.
25748447 2015 Sphingosine-1-phosphate induces the migration of thyroid follicular carcinoma cells through the microRNA-17/PTK6/ERK1/2 pathway.
25733683 2015 Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.
25416956 2014 A proteome-scale map of the human interactome network.
25377660 2014 Downregulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma.
25241146 2015 Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression in vivo.
25153721 2014 PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.
25019382 2014 HIF-1?-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion.
24788754 2014 PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.
24728074 2014 Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome.
24523872 2014 BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
23928995 2013 Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression.
23856248 2013 PTK6 activation at the membrane regulates epithelial-mesenchymal transition in prostate cancer.
23814047 2013 Protein-tyrosine phosphatase 1B antagonized signaling by insulin-like growth factor-1 receptor and kinase BRK/PTK6 in ovarian cancer cells.
23758975 2013 Protein tyrosine kinase 6 is associated with nasopharyngeal carcinoma poor prognosis and metastasis.
23707532 2013 HER2 regulates Brk/PTK6 stability via upregulating calpastatin, an inhibitor of calpain.
23535732 2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
23497344 2013 Low expression of PTK6/Brk predicts poor prognosis in patients with laryngeal squamous cell carcinoma.
23352614 2013 PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation.
23291984 2013 Brk/PTK6 cooperates with HER2 and Src in regulating breast cancer cell survival and epithelial-to-mesenchymal transition.
23027128 2013 Protein tyrosine kinase 6 protects cells from anoikis by directly phosphorylating focal adhesion kinase and activating AKT.
22989419 2012 Targeting protein tyrosine kinase 6 enhances apoptosis of colon cancer cells following DNA damage.
22849407 2012 Hsp90 rescues PTK6 from proteasomal degradation in breast cancer cells.
22705009 2012 Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma.
22547065 2012 Suppressor of cytokine signaling 3 inhibits breast tumor kinase activation of STAT3.
22231447 2012 Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR.
22084245 2012 Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 CRK-associated substrate.
21923922 2011 Mammary gland specific expression of Brk/PTK6 promotes delayed involution and tumor formation associated with activation of p38 MAPK.
21603980 2011 Detection of Brk expression in non-small cell lung cancer: clinicopathological relevance.
21479203 2011 The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of ?-catenin.
21380407 2011 Impact of protein tyrosine kinase 6 (PTK6) on human epidermal growth factor receptor (HER) signalling in breast cancer.
21240512 2011 Breast tumor kinase (Brk/PTK6) plays a role in the differentiation of primary keratinocytes.
20929863 2010 Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.
20700126 2010 In situ quantification of HER2-protein tyrosine kinase 6 (PTK6) protein-protein complexes in paraffin sections from breast cancer tissues.
20687930 2010 Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20606012 2010 Protein tyrosine kinase 6 directly phosphorylates AKT and promotes AKT activation in response to epidermal growth factor.
20554524 2010 PTK6 inhibits down-regulation of EGF receptor through phosphorylation of ARAP1.
20193745 2010 Building a better understanding of the intracellular tyrosine kinase PTK6 - BRK by BRK.
20162673 2010 Deregulation of the cell cycle by breast tumor kinase (Brk).
20026641 2010 Identification of beta-catenin as a target of the intracellular tyrosine kinase PTK6.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19661439 2009 Brk protects breast cancer cells from autophagic cell death induced by loss of anchorage.
19621240 2009 Overexpression of PTK6 (breast tumor kinase) protein--a prognostic factor for long-term breast cancer survival--is not due to gene amplification.
19439179 2009 BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest.
19401189 2009 Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6.
19393627 2009 STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation.
19304789 2009 Oncogenic functions of PTK6 are enhanced by its targeting to plasma membrane but abolished by its targeting to nucleus.
18829532 2008 Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion.
18781181 2008 Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients.
18719096 2008 Brk is coamplified with ErbB2 to promote proliferation in breast cancer.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18296648 2008 Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma.
18077133 2008 Breast tumor kinase BRK requires kinesin-2 subunit KAP3A in modulation of cell migration.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17997837 2007 Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6.
17910947 2007 Identification of twinfilin-2 as a factor involved in neurite outgrowth by RNAi-based screen.
17822667 2007 Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
16651629 2006 Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes.
16568091 2006 Identification of STAT3 as a specific substrate of breast tumor kinase.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16179349 2005 Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression.
15961400 2005 An intramolecular interaction between SH2-kinase linker and kinase domain is essential for the catalytic activity of protein-tyrosine kinase-6.
15951569 2005 Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules.
15870689 2005 Interaction between Brk kinase and insulin receptor substrate-4.
15572663 2004 Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin.
15539407 2005 Regulated association of protein kinase B/Akt with breast tumor kinase.
15509496 2004 Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15471878 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.
15056653 2004 Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14676834 2004 Role of the Brk SH3 domain in substrate recognition.
12833144 2003 Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells.
12725532 2003 Brk, Srm, Frk, and Src42A form a distinct family of intracellular Src-like tyrosine kinases.
12482964 2003 Sam68 enhances the cytoplasmic utilization of intron-containing RNA and is functionally regulated by the nuclear kinase Sik/BRK.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12297019 2002 Purification and spectroscopic characterization of the human protein tyrosine kinase-6 SH3 domain.
12121988 2002 Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition.
11997104 2002 Characterization of the 5'-flanking region of the human PTK6 gene.
11780052 2001 The DNA sequence and comparative analysis of human chromosome 20.
11330822 2001 Complete sequence-specific 1H, 13C and 15N resonance assignments of the human PTK6 SH2 domain.
11114724 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.
10980601 2000 A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK.
10913193 2000 Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability.
10430081 1999 BRK/Sik expression in the gastrointestinal tract and in colon tumors.
9749526 1998 Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase.
9333026 1997 Characterisation and chromosome mapping of the human non receptor tyrosine kinase gene, brk.
9284935 1997 Assignment of the human PTK6 gene encoding a non-receptor protein tyrosine kinase to 20q13.3 by fluorescence in situ hybridization.
9185712 1997 Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma.
8940083 1996 Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor.
8247543 1993 A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes.
8036022 1994 Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours.