ArticleiScience2021
Signaling Heterogeneity is Defined by Pathway Architecture and Intercellular Variability in Protein Expression.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- The diversification of methods for studying cell-cell interactions and communication.Nature reviews. Genetics · 2024Review
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- The ability to sense the environment is heterogeneously distributed in cell populations.eLife · 2024Article
- Oscillatory ERK Signaling and Morphology Determine Heterogeneity of Breast Cancer Cell Chemotaxis via MEK-ERK and p38-MAPK Signaling Pathways.Bioengineering (Basel, Switzerland) · 2023Article
- A high-content endogenous GLUT4 trafficking assay reveals new aspects of adipocyte biology.Life science alliance · 2023Article
- Meta-Dynamic Network Modelling for Biochemical Networks.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The Role of Insulin-like Peptide in Maintaining Hemolymph Glucose Homeostasis in the Pacific White ShrimpInternational journal of molecular sciences · 2022Article
- Feature selection revisited in the single-cell era.Genome biology · 2021Review
- Dynamic modelling of the PI3K/MTOR signalling network uncovers biphasic dependence of mTORC1 activity on the mTORC2 subunit SIN1.PLoS computational biology · 2021Article
- Article
- Non-synaptic Cell-Autonomous Mechanisms Underlie Neuronal Hyperactivity in a Genetic Model ofFrontiers in molecular neuroscience · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin's activation of PI3K/Akt signaling, stimulates glucose uptake by enhancing delivery of GLUT4 to the cell surface. Here we examined the origins of intercellular heterogeneity in insulin signaling. Akt activation alone accounted for ~25% of the variance in GLUT4, indicating that additional sources of variance exist. The Akt and GLUT4 responses were highly reproducible within the same cell, suggesting the variance is between cells (extrinsic) and not within cells (intrinsic). Generalized mechanistic models (supported by experimental observations) demonstrated that the correlation between the steady-state levels of two measured signaling processes decreases with increasing distance from each other and that intercellular variation in protein expression (as an example of extrinsic variance) is sufficient to account for the variance in and between Akt and GLUT4. Thus, the response of a population to insulin signaling is underpinned by considerable single-cell heterogeneity that is largely driven by variance in gene/protein expression between cells.
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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 OpenQuestion graph.