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Mathematical model of phosphatidylinositol-4,5-bisphosphate hydrolysis mediated by epidermal growth factor receptor generating diacylglycerol

Paper ID Volume ID Publish Year Pages File Format Full-Text
25719 43593 2006 18 PDF Available
Title
Mathematical model of phosphatidylinositol-4,5-bisphosphate hydrolysis mediated by epidermal growth factor receptor generating diacylglycerol
Abstract

Phosphatidylinositol-4,5-bisphosphate (PIP2) is hydrolyzed in response to the tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and plays an important role in regulating cell proliferation and differentiation through the generation of second messengers diacylglycerol (DAG) and trisphosphate inositol (IP3) which lead to the activation of protein kinase C (PKC) and increased levels of intracellular calcium, respectively. In the paper, a mathematical model was established to simulate the accumulation of DAG due to PIP2 hydrolysis mediated by EGFR. Molecular mechanisms between DAG, PIP2, EGFR and phosphatidylinositol transfer protein (PITP) were explained successfully, and positive cooperativity which existed between phospholipase C-gamma1 (PLC-γ1) and PIP2 was also explained. In the model the effects of parameters on simulation of PIP2 hydrolysis were analyzed and the efficacies of some molecular intervention strategies were predicted.To test the coherence between the model and the biological response to epidermal growth factor (EGF) in cells, the levels of DAG and the tyrosine phosphorylation-EGFRs in NIH3T3 mouse embryonic fibroblast (MEF) were determined by biochemical experiments which showed that the accumulation of DAG was a sigmoidal function of phosphorylation-EGFR concentration, and the consistency between the mathematical model and experimental results was confirmed.In brief, this mathematical model provided a new idea for the further study of the dynamic change of biological characteristics in inositol phospholipid hydrolysis, predicting the efficacy of molecular intervention and the relationship between the metabolisms of inositol phospholipid and other signal transduction pathways.

Keywords
DAG, diacylglycerol; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulation kinase; PIP2, phosphatidylinositol-4,5-bisphosphate; IP3, trisphosphate inositol; PI, phosphatidylinositol; PA, phosphatidic ac
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Mathematical model of phosphatidylinositol-4,5-bisphosphate hydrolysis mediated by epidermal growth factor receptor generating diacylglycerol
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 124, Issue 3, 25 July 2006, Pages 574–591
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us