ArticleScience signaling2013
Tyrosine kinase BMX phosphorylates phosphotyrosine-primed motif mediating the activation of multiple receptor tyrosine kinases.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 23 citations in OpenAlex.
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Bone marrow kinase X-linked in pulmonary diseases: pathogenic gene, diagnostic biomarker, and treatment target-a narrative review.Translational pediatrics · 2026Review
- Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.Journal of medicinal chemistry · 2026Article
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Discovery of Dihydropyrimido-Pyrimidine-Based Bone Marrow Tyrosine Kinase Gene in Chromosome X Protein Proteolysis-Targeting Chimeras for the Treatment of Prostate Cancer.ACS medicinal chemistry letters · 2026Article
- Inhibition of tyrosine kinase BMX increases cell death in response to existing chemotherapeutic agents overcoming apoptotic resistance in cancer.Cell death & disease · 2025Article
- Structural Identification of Major Molecular Determinants for Phosphotyrosine Recognition in Tyrosine Kinases Reveals Tumour Promoting and Suppressive Functions.bioRxiv : the preprint server for biology · 2025Article
- Article
- BMX controls 3βHSD1 and sex steroid biosynthesis in cancer.The Journal of clinical investigation · 2023Article
- AR-dependent phosphorylation and phospho-proteome targets in prostate cancer.Endocrine-related cancer · 2020Review
- Substrate priming enhances phosphorylation by the budding yeast kinases Kin1 and Kin2.The Journal of biological chemistry · 2018Article
- BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer.Cancer research · 2018Article
- Hypoxia Reporter Element Assay.Bio-protocol · 2018Article
- Homing in: Mechanisms of Substrate Targeting by Protein Kinases.Trends in biochemical sciences · 2018Review
- Hypoxia-induced upregulation of BMX kinase mediates therapeutic resistance in acute myeloid leukemia.The Journal of clinical investigation · 2018Article
- EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells.Oncotarget · 2016Article
- EGF-receptor specificity for phosphotyrosine-primed substrates provides signal integration with Src.Nature structural & molecular biology · 2015Article
- Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Urotensin-II receptor stimulation of cardiac L-type Ca2+ channels requires the βγ subunits of Gi/o-protein and phosphatidylinositol 3-kinase-dependent protein kinase C β1 isoform.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The nonreceptor tyrosine kinase BMX (bone marrow tyrosine kinase gene on chromosome X) is abundant in various cell types and activated downstream of phosphatidylinositol-3 kinase (PI3K) and the kinase Src, but its substrates are unknown. Positional scanning peptide library screening revealed a marked preference for a priming phosphorylated tyrosine (pY) in the -1 position, indicating that BMX substrates may include multiple tyrosine kinases that are fully activated by pYpY sites in the kinase domain. BMX phosphorylated focal adhesion kinase (FAK) at Tyr⁵⁷⁷ subsequent to its Src-mediated phosphorylation at Tyr⁵⁷⁶. Loss of BMX by RNA interference or by genetic deletion in mouse embryonic fibroblasts (MEFs) markedly impaired FAK activity. Phosphorylation of the insulin receptor in the kinase domain at Tyr¹¹⁸⁹ and Tyr¹¹⁹⁰, as well as Tyr¹¹⁸⁵, and downstream phosphorylation of the kinase AKT at Thr³⁰⁸ were similarly impaired by BMX deficiency. However, insulin-induced phosphorylation of AKT at Ser⁴⁷³ was not impaired in Bmx knockout MEFs or liver tissue from Bmx knockout mice, which also showed increased insulin-stimulated glucose uptake, possibly because of decreased abundance of the phosphatase PHLPP (PH domain leucine-rich repeat protein phosphatase). Thus, by identifying the pYpY motif as a substrate for BMX, our findings suggest that BMX functions as a central regulator among multiple signaling pathways mediated by tyrosine kinases.
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