ArticleOncogene2004
Role of the Brk SH3 domain in substrate recognition.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.medRxiv : the preprint server for health sciences · 2024Article
- In Silico Screening of Multi-Domain Targeted Inhibitors for PTK6: A Strategy Integrating Drug Repurposing and Consensus Docking.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Review
- Review
- Designer installation of a substrate recruitment domain to tailor enzyme specificity.Nature chemical biology · 2023Article
- Biochemical Studies of Systemic Lupus Erythematosus-Associated Mutations in Nonreceptor Tyrosine Kinases Ack1 and Brk.Biochemistry · 2023Article
- Review
- Allosteric regulation and inhibition of protein kinases.Biochemical Society transactions · 2023Review
- Shank3 related muscular hypotonia is accompanied by increased intracellular calcium concentrations and ion channel dysregulation in striated muscle tissue.Frontiers in cell and developmental biology · 2023Article
- TRAF3 in T Cells Restrains Negative Regulators of LAT to Promote TCR/CD28 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- 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 · 2021Article
- Putting the BRK on breast cancer: From molecular target to therapeutics.Theranostics · 2021Review
- Targeting protein tyrosine kinase 6 in cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Bif-1 Interacts with Prohibitin-2 to Regulate Mitochondrial Inner Membrane during Cell Stress and Apoptosis.Journal of the American Society of Nephrology : JASN · 2019Article
- Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase.The Journal of biological chemistry · 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
- 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
- Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR.Oncogene · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Breast tumor kinase (Brk) is a nonreceptor tyrosine kinase that is overexpressed in a high percentage of breast carcinomas. Brk contains SH3, SH2, and tyrosine kinase catalytic domains in a similar arrangement as Src family kinases. In this study, we explored the roles of the SH3 and SH2 domains in Brk regulation and substrate binding. We introduced a series of mutations into Brk that were predicted to disrupt the intramolecular interactions involving the SH3 and SH2 domains. These mutant forms of Brk displayed higher activity than wild-type Brk when expressed in human embryonic kidney HEK293 cells. These studies also allowed us to pinpoint the intramolecular binding site for the SH3 domain. To examine substrate binding, we compared binding and phosphorylation of Sam68, a physiological substrate of Brk. These experiments showed that the SH3 domain plays a particularly important role in substrate recognition. We confirmed this conclusion using a series of synthetic peptides in which a substrate sequence was coupled to an SH3 or SH2 ligand. The SH3-binding substrate had a significantly lower K(m) than a control, while no difference was observed between an SH2-binding substrate and a control. Taken together, our data suggest that SH3 interactions will govern phosphorylation of many substrates by Brk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.