Covering a broad dynamic range: information processing at the erythropoietin receptor.


Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and experimental validation that rapid ligand depletion and replenishment of the cell surface receptor are characteristic features of the erythropoietin (Epo) receptor (EpoR). The amount of Epo-EpoR complexes and EpoR activation integrated over time corresponds linearly to ligand input; this process is carried out over a broad range of ligand concentrations. This relation depends solely on EpoR turnover independent of ligand binding, which suggests an essential role of large intracellular receptor pools. These receptor properties enable the system to cope with basal and acute demand in the hematopoietic system.


PubMed ID: 20488988

Projects: SBEpo - Systems Biology of Erythropoietin

Publication type: Journal

Journal: Science

Citation: Science. 2010 Jun 11;328(5984):1404-8. doi: 10.1126/science.1184913. Epub 2010 May 20.

Date Published: 11th Jun 2010

Registered Mode: Not specified

Authors: V. Becker, M. Schilling, J. Bachmann, U. Baumann, A. Raue, T. Maiwald, J. Timmer, U. Klingmuller

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Views: 3624

Created: 13th Oct 2016 at 13:24

Last updated: 3rd Aug 2020 at 18:36

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