ArticleMolecular systems biology2011
Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range.
Article in Molecular systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 116 citations in OpenAlex.
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- IFN-γ inhibits ovarian cancer progression via SOCS1/JAK/STAT signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Relationship Between Dimensionality and Convergence of Optimization Algorithms: A Comparison Between Data-Driven Normalization and Scaling Factor-Based Methods Using PEPSSBI.Methods in molecular biology (Clifton, N.J.) · 2022Article
- STAT5 as a Key Protein of Erythropoietin Signalization.International journal of molecular sciences · 2021Review
- Increased expression of IFN-γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop.Experimental and therapeutic medicine · 2021Article
- Parameterization of mechanistic models from qualitative data using an efficient optimal scaling approach.Journal of mathematical biology · 2020Article
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Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. The specific contributions of individual feedback regulators, however, remain unclear. Based on extensive time-resolved data sets in primary erythroid progenitor cells, we established a dynamic pathway model to dissect the roles of the two transcriptional negative feedback regulators of the suppressor of cytokine signaling (SOCS) family, CIS and SOCS3, in JAK2/STAT5 signaling. Facilitated by the model, we calculated the STAT5 response for experimentally unobservable Epo concentrations and provide a quantitative link between cell survival and the integrated response of STAT5 in the nucleus. Model predictions show that the two feedbacks CIS and SOCS3 are most effective at different ligand concentration ranges due to their distinct inhibitory mechanisms. This divided function of dual feedback regulation enables control of STAT5 responses for Epo concentrations that can vary 1000-fold in vivo. Our modeling approach reveals dose-dependent feedback control as key property to regulate STAT5-mediated survival decisions over a broad range of ligand concentrations.
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