ArticlePloS one2011
The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of β-catenin.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2022Article
- Article
- Targeting protein tyrosine kinase 6 in cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Protein tyrosine kinase 6 signaling in prostate cancer.American journal of clinical and experimental urology · 2020Review
- Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells.Molecular cancer research : MCR · 2018Article
- Cross-Species Genome-Wide Identification of Evolutionary Conserved MicroProteins.Genome biology and evolution · 2017Article
- Signature of positive selection of PTK6 gene in East Asian populations: a cross talk for Helicobacter pylori invasion and gastric cancer endemicity.Molecular genetics and genomics : MGG · 2015Article
- Cancer-Associated Mutations in Breast Tumor Kinase/PTK6 Differentially Affect Enzyme Activity and Substrate Recognition.Biochemistry · 2015Article
- Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.Molecular and cellular biology · 2015Article
- PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.Oncotarget · 2014Article
- Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy.World journal of clinical oncology · 2014Review
- PTK6 activation at the membrane regulates epithelial-mesenchymal transition in prostate cancer.Cancer research · 2013Article
- Context-specific protein tyrosine kinase 6 (PTK6) signalling in prostate cancer.European journal of clinical investigation · 2013Review
- Targeting protein tyrosine kinase 6 enhances apoptosis of colon cancer cells following DNA damage.Molecular cancer therapeutics · 2012Article
- Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 CRK-associated substrate.The Journal of biological chemistry · 2012Article
- Wnt and SHH in prostate cancer: trouble mongers occupy the TRAIL towards apoptosis.Cell proliferation · 2011Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Protein tyrosine kinase 6 (PTK6), also called breast tumor kinase (BRK), is expressed in epithelial cells of various tissues including the prostate. Previously it was shown that PTK6 is localized to epithelial cell nuclei in normal prostate, but becomes cytoplasmic in human prostate tumors. PTK6 is also primarily cytoplasmic in the PC3 prostate adenocarcinoma cell line. Sequencing revealed expression of wild type full-length PTK6 transcripts in addition to an alternative transcript lacking exon 2 in PC3 cells. The alternative transcript encodes a 134 amino acid protein, referred to here as ALT-PTK6, which shares the first 77 amino acid residues including the SH3 domain with full length PTK6. RT-PCR was used to show that ALT-PTK6 is coexpressed with full length PTK6 in established human prostate and colon cell lines, as well as in primary cell lines derived from human prostate tissue and tumors. Although interaction between full-length PTK6 and ALT-PTK6 was not detected, ALT-PTK6 associates with the known PTK6 substrates Sam68 and β-catenin in GST pull-down assays. Coexpression of PTK6 and ALT-PTK6 led to suppression of PTK6 activity and reduced association of PTK6 with tyrosine phosphorylated proteins. While ALT-PTK6 alone did not influence β-catenin/TCF transcriptional activity in a luciferase reporter assay, it enhanced PTK6-mediated inhibition of β-catenin/TCF transcription by promoting PTK6 nuclear functions. Ectopic expression of ALT-PTK6 led to reduced expression of the β-catenin/TCF targets Cyclin D1 and c-Myc in PC3 cells. Expression of tetracycline-inducible ALT-PTK6 blocked the proliferation and colony formation of PC3 cells. Our findings suggest that ALT-PTK6 is able to negatively regulate growth and modulate PTK6 activity, protein-protein associations and/or subcellular localization. Fully understanding functions of ALT-PTK6 and its impact on PTK6 signaling will be critical for development of therapeutic strategies that target PTK6 in cancer.
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