ArticleThe Journal of biological chemistry2009
Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 57 citations in OpenAlex.
- DeepPhosPPI: a deep learning framework with attention-CNN and transformer for predicting phosphorylation effects on protein-protein interactions.Briefings in bioinformatics · 2025Article
- A web portal for exploring kinase-substrate interactions.NPJ systems biology and applications · 2024Article
- Network-driven cancer cell avatars for combination discovery and biomarker identification for DNA damage response inhibitors.NPJ systems biology and applications · 2024Article
- 14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.Cell reports · 2024Article
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- Unraveling the harmful effect of oxidative stress on male fertility: A mechanistic insight.Frontiers in endocrinology · 2023Review
- PTMint database of experimentally verified PTM regulation on protein-protein interaction.Bioinformatics (Oxford, England) · 2023Article
- Review
- Emerging role of BAD and DAD1 as potential targets and biomarkers in cancer.Oncology letters · 2021Review
- Vitamin E Delivery Systems Increase Resistance to Oxidative Stress in Red Deer Sperm Cells: Hydrogel and Nanoemulsion Carriers.Antioxidants (Basel, Switzerland) · 2021Article
- Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease.Life (Basel, Switzerland) · 2021Review
- CIGB-300 anticancer peptide regulates the protein kinase CK2-dependent phosphoproteome.Molecular and cellular biochemistry · 2020Article
- Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study.Scientific reports · 2020Article
- Expression of the BAD pathway is a marker of triple-negative status and poor outcome.Scientific reports · 2019Article
- The impact of phosphatases on proliferative and survival signaling in cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Design and Profiling of a Subcellular Targeted Optogenetic cAMP-Dependent Protein Kinase.Cell chemical biology · 2018Article
- BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion.Experimental cell research · 2015Article
- PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.Theranostics · 2014Review
- 14-3-3 proteins are essential signalling hubs for beta cell survival.Diabetologia · 2013Article
- Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis.Cell death & disease · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BAD is a proapoptotic member of the Bcl-2 protein family that is regulated by phosphorylation in response to survival factors. Although much attention has been devoted to the identification of phosphorylation sites in murine BAD, little data are available with respect to phosphorylation of human BAD protein. Using mass spectrometry, we identified here besides the established phosphorylation sites at serines 75, 99, and 118 several novel in vivo phosphorylation sites within human BAD (serines 25, 32/34, 97, and 124). Furthermore, we investigated the quantitative contribution of BAD targeting kinases in phosphorylating serine residues 75, 99, and 118. Our results indicate that RAF kinases represent, besides protein kinase A, PAK, and Akt/protein kinase B, in vivo BAD-phosphorylating kinases. RAF-induced phosphorylation of BAD was reduced to control levels using the RAF inhibitor BAY 43-9006. This phosphorylation was not prevented by MEK inhibitors. Consistently, expression of constitutively active RAF suppressed apoptosis induced by BAD and the inhibition of colony formation caused by BAD could be prevented by RAF. In addition, using the surface plasmon resonance technique, we analyzed the direct consequences of BAD phosphorylation by RAF with respect to association with 14-3-3 and Bcl-2/Bcl-X(L) proteins. Phosphorylation of BAD by active RAF promotes 14-3-3 protein association, in which the phosphoserine 99 represented the major binding site. Finally, we show here that BAD forms channels in planar bilayer membranes in vitro. This pore-forming capacity was dependent on phosphorylation status and interaction with 14-3-3 proteins. Collectively, our findings provide new insights into the regulation of BAD function by phosphorylation.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.