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

Journal of Biotechnology
Yong-chun SuQin-kai Deng

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-gamma1) 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 th...Continue Reading

References

Jan 1, 1992·Cold Spring Harbor Symposia on Quantitative Biology·T HunterP van der Geer
May 1, 1997·Biophysical Journal·J M Haugh, D A Lauffenburger
Jun 13, 1997·The Journal of Biological Chemistry·S G Rhee, Y S Bae
Mar 1, 1997·The International Journal of Biochemistry & Cell Biology·J J Hsuan, S H Tan
Jan 15, 1999·Science·U S Bhalla, R Iyengar
Apr 1, 1999·Biotechnology and Bioengineering·B N KholodenkoJ Schwaber
Apr 2, 1999·Science·G WengR Iyengar
Oct 9, 1999·The Journal of Biological Chemistry·B N KholodenkoJ B Hoek
Nov 24, 1999·The Journal of Biological Chemistry·J M HaughD A Lauffenburger
Oct 4, 2000·Physiological Reviews·M J Rebecchi, S N Pentyala
Jun 8, 2001·Annual Review of Biochemistry·S G Rhee
Sep 22, 2001·Biophysical Journal·S Y ShvartsmanD A Lauffenburger
Dec 26, 2001·Biophysical Journal·Karin A ReijengaJacky L Snoep
Mar 5, 2002·European Journal of Biochemistry·Stefan SchusterThomas Höfer
Mar 26, 2002·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Hidde de Jong
Apr 5, 2002·The Biochemical Journal·Xiao-Chun BaiShen-Qiu Luo
Sep 12, 2002·Cellular and Molecular Life Sciences : CMLS·A M MartelliL Cocco
Nov 15, 2002·Nature·Albert Goldbeter
Nov 15, 2002·Nature·Timothy G Buchman
Dec 14, 2002·Trends in Cell Biology·H Steven WileyDouglas A Lauffenburger
Jan 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Peter KleinJoseph Schlessinger

❮ Previous
Next ❯

Citations

Jul 21, 2011·Canadian Journal of Microbiology·Ana Paula de Figueiredo Conte VanzelaRolf Alexander Prade
Feb 11, 2018·FEBS Letters·Rohit SuratekarSandeep Krishna
Jan 15, 2019·Biochemical and Biophysical Research Communications·Madison A KennedyChristal D Sohl

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.