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Nat Rev Mol Cell Biol. 2011 Feb;12(2):104-17. doi: 10.1038/nrm3048.

Feedback regulation of EGFR signalling: decision making by early and delayed loops.

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Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.


Human-made information relay systems invariably incorporate central regulatory components, which are mirrored in biological systems by dense feedback and feedforward loops. This type of system control is exemplified by positive and negative feedback loops (for example, receptor endocytosis and dephosphorylation) that enable growth factors and receptor Tyr kinases of the epidermal growth factor receptor (EGFR)/ERBB family to regulate cellular function. Recent studies show that the collection of feedback regulatory loops can perform computational tasks - such as decoding ligand specificity, transforming graded input signals into a digital output and regulating response kinetics. Aberrant signal processing and feedback regulation can lead to defects associated with pathologies such as cancer.

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