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BMC Cell Biology

, 6:41

First Online: 30 November 2005Received: 02 August 2005Accepted: 30 November 2005

Abstract

BackgroundThe ErbB family of receptors are dysregulated in a number of cancers, and the signaling pathway of this receptor family is a critical target for several anti-cancer drugs. Therefore a detailed understanding of the mechanisms of receptor activation is critical. However, despite a plethora of biochemical studies and recent single particle tracking experiments, the early molecular mechanisms involving epidermal growth factor EGF binding and EGF receptor EGFR dimerization are not as well understood. Herein, we describe a spatially distributed Monte Carlo based simulation framework to enable the simulation of in vivo receptor diffusion and dimerization.

ResultsOur simulation results are in agreement with the data from single particle tracking and biochemical experiments on EGFR. Furthermore, the simulations reveal that the sequence of receptor-receptor and ligand-receptor reaction events depends on the ligand concentration, receptor density and receptor mobility.

ConclusionOur computer simulations reveal the mechanism of EGF binding on EGFR. Overall, we show that spatial simulation of receptor dynamics can be used to gain a mechanistic understanding of receptor activation which may in turn enable improved cancer treatments in the future.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-6-41 contains supplementary material, which is available to authorized users.

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Author: Kapil Mayawala - Dionisios G Vlachos - Jeremy S Edwards

Source: https://link.springer.com/article/10.1186/1471-2121-6-41







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