Please use this identifier to cite or link to this item: https://doi.org/10.1126/science.1181729
Title: Restriction of receptor movement alters cellular response: Physical force sensing by EphA2
Authors: Salaita, K.
Nair, P.M.
Petit, R.S.
Neve, R.M.
Das, D.
Gray, J.W.
GROVES,IV, JOHN TAYLOR 
Issue Date: 12-Mar-2010
Citation: Salaita, K., Nair, P.M., Petit, R.S., Neve, R.M., Das, D., Gray, J.W., GROVES,IV, JOHN TAYLOR (2010-03-12). Restriction of receptor movement alters cellular response: Physical force sensing by EphA2. Science 327 (5971) : 1380-1385. ScholarBank@NUS Repository. https://doi.org/10.1126/science.1181729
Abstract: Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying Laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.
Source Title: Science
URI: http://scholarbank.nus.edu.sg/handle/10635/128711
ISSN: 00368075
DOI: 10.1126/science.1181729
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