A Computer‐Based Model for the Regulation of Mitogen Activated Protein Kinase (MAPK) Activation
- 1 January 2003
- journal article
- Published by Taylor & Francis in Journal of Receptors and Signal Transduction
- Vol. 23 (2-3) , 197-209
- https://doi.org/10.1081/rrs-120025203
Abstract
Computer simulations and mathematical modeling of biological processes are becoming increasingly popular, and yet the complexity of the biochemical systems or the differences between experimental setups make it very difficult to establish a standard formula for these modeling projects. Before we can start using computer-based models for predictions or targeted experiment designs, it is very important to establish a reliable model on which those predictions can be based and experimentally tested. Here we attempt to present a computer model for the mitogen-activated protein kinase (MAPK) signaling cascade which is consistent with previously published experimental results. In this study we have focused our attention to a generic MAPK ERK (extracellular signal-regulated kinase) pathway activated by epidermal growth factor (EGF) in an attempt to understand how receptors may achieve different activation kinetics of the MAPK signaling. We successfully show that the level of receptor expression is one key determinant in this regulation, and that the binding affinity of the active receptor to adaptor proteins can have a small but albeit direct effect on the downstream activation.Keywords
This publication has 37 references indexed in Scilit:
- Potential roles of extracellular signal-regulated kinase but not p38 during myeloid differentiation of U937 cells stimulated by cytokines: Augmentation of differentiation via prolonged activation of extracellular signal-regulated kinaseExperimental Hematology, 2002
- The JNK signal transduction pathwayPublished by Elsevier ,2002
- Requirement for Sustained MAPK Signaling in Both CD4 and CD8 Lineage Commitment: A Threshold ModelCellular Immunology, 2001
- Mammalian MAP kinase signalling cascadesNature, 2001
- A functional role of mitogen-activated protein kinases, Erk1 and Erk2, in the differentiation of a human leukemia cell line, UT-7/GM: A possible key factor for cell fate determination toward erythroid and megakaryocytic lineagesInternational Journal of Hematology, 2001
- Interaction of EGF receptor and Grb2 in living cells visualized by fluorescence resonance energy transfer (FRET) microscopyCurrent Biology, 2000
- Megakaryocyte Growth and Development Factor-Induced Proliferation and Differentiation Are Regulated by the Mitogen-Activated Protein Kinase Pathway in Primitive Cord Blood Hematopoietic ProgenitorsBlood, 1999
- Sustained Activation of the Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase Pathway Is Required for Megakaryocytic Differentiation of K562 CellsPublished by Elsevier ,1997
- Activation of Epidermal Growth Factor Receptor by Epidermal Growth FactorBiochemistry, 1996
- Signal transmission by epidermal growth factor receptor: coincidence of activation and dimerizationBiochemistry, 1992