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The agent-based and rule-based approach permits consideration of combinatorial complexity, a problem associated with multiple phosphorylation sites and the potential for simultaneous binding of adaptors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The model was used to simulate recruitment of four different signaling molecules (Grb2, PLC\u03b31, Stat5, Shc) to the phosphorylated EGFR tail, with rules based on coarse-grained prediction of spatial constraints. Parameters were derived in part from quantitative immunoblotting, immunoprecipitation and electron microscopy data. Results demonstrate that receptor clustering increases the efficiency of individual adaptor retainment on activated EGFR, an effect that is overridden if crowding is imposed by receptor overexpression. Simultaneous docking of multiple proteins is highly dependent on receptor-adaptor stability and independent of clustering.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Overall, we propose that receptor density, reaction kinetics and membrane spatial organization all contribute to signaling efficiency and influence the carcinogenesis process.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-57","type":"journal-article","created":{"date-parts":[[2010,5,6]],"date-time":"2010-05-06T18:13:54Z","timestamp":1273169634000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Spatio-temporal modeling of signaling protein recruitment to EGFR"],"prefix":"10.1186","volume":"4","author":[{"given":"Ming-yu","family":"Hsieh","sequence":"first","affiliation":[]},{"given":"Shujie","family":"Yang","sequence":"additional","affiliation":[]},{"given":"Mary Ann","family":"Raymond-Stinz","sequence":"additional","affiliation":[]},{"given":"Jeremy S","family":"Edwards","sequence":"additional","affiliation":[]},{"given":"Bridget S","family":"Wilson","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,5,6]]},"reference":[{"key":"446_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/35077225","volume":"411","author":"P Blume-Jensen","year":"2001","unstructured":"Blume-Jensen P, Hunter T: Oncogenic kinase signalling. 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