ArticlePLoS computational biology2014
Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
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- Long-term Effects of the Janus Kinase 1/2 Inhibitor Ruxolitinib on Pulmonary Hypertension and the Cardiac Function in a Patient with Myelofibrosis.Internal medicine (Tokyo, Japan) · 2020Article
- TRAIL-induced variation of cell signaling states provides nonheritable resistance to apoptosis.Life science alliance · 2019Article
- Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.Genome biology · 2018Article
- Somatotropic Axis Regulation Unravels the Differential Effects of Nutritional and Environmental Factors in Growth Performance of Marine Farmed Fishes.Frontiers in endocrinology · 2018Review
- Tissue-specific tumorigenesis: context matters.Nature reviews. Cancer · 2017Review
- HIPPIE v2.0: enhancing meaningfulness and reliability of protein-protein interaction networks.Nucleic acids research · 2017Article
- The organelle of differentiation in embryos: the cell state splitter.Theoretical biology & medical modelling · 2016Review
- Cell type-specific properties and environment shape tissue specificity of cancer genes.Scientific reports · 2016Article
- Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.Oncotarget · 2015Article
- Tuneable endogenous mammalian target complementation via multiplexed plasmid-based recombineering.Scientific reports · 2015Article
- Identification of reproducible drug-resistance-related dysregulated genes in small-scale cancer cell line experiments.Scientific reports · 2015Article
- Dissecting the calcium-induced differentiation of human primary keratinocytes stem cells by integrative and structural network analyses.PLoS computational biology · 2015Article
- Cell-type specific photoreceptors and light signaling pathways in the multicellular green alga Volvox carteri and their potential role in cellular differentiation.Plant signaling & behavior · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors) and the output (transcription factors) layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.
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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.