Affinity Regulates Spatial Range of EGF Receptor Autocrine Ligand Binding
Proper spatial localization of EGFR signaling activated by autocrine ligands represents a critical factor in embryonic development as well as tissue organization and function, and ligand/receptor binding affinity is among the molecular and cellular properties suggested to play a role in governing this localization. The authors employ a computational model to predict how receptor-binding affinity affects local capture of autocrine ligand vis-a-vis escape to distal regions, and provide experimental test by constructing cell lines expressing EGFR along with either wild-type EGF or a low-affinity mutant, EGF{sup L47M}. The model predicts local capture of a lower affinity autocrine ligand to be less efficient when the ligand production rate is small relative to receptor appearance rate. The experimental data confirm this prediction, demonstrating that cells can use ligand/receptor binding affinity to regulate ligand spatial distribution when autocrine ligand production is limiting for receptor signaling.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- US Department of Energy (US)
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 15011381
- Report Number(s):
- PNNL-SA-41390; DEBIAO; TRN: US200506%%418
- Journal Information:
- Developmental Biology, Vol. 250, Issue 2; Other Information: PBD: 8 Aug 2002; ISSN 0012-1606
- Country of Publication:
- United States
- Language:
- English
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