Dataset Information

Gex-Fabry1984 - model of receptor-mediated endocytosis of EGF in BALB/c 3T3 cells

ABSTRACT: We present a mathematical model for analyzing, simulating, and quantitating the dynamic and steady-state characteristics of receptor-mediated endocytosis. The basic processes considered by the model are ligand-receptor binding, diffusion of receptors and ligand-receptor complexes in the plane of the membrane toward and away from coated pits, binding of ligand-receptor complexes to coated pit proteins, endocytosis of coated pit contents, degradation of ligand, and recycling of undegraded receptors. The model accounts quantitatively for a wide variety of kinetic data and makes new predictions about steady-state characteristics. We show that for homogeneous receptors the slope of the Scatchard plot is not necessarily constant but can have a positive or negative derivative, depending on the concentration of coated pit proteins and their reactivity. This finding suggests that binding data, which show linear and concave curves, might be explainable be a simple coated pit-related mechanism. Similarly the relationship between the x-intercept and the number of receptors is also affected by kinetic parameters controlling endocytosis. We briefly discuss these results in terms of possible mechanisms for the action of tumor promoters, the large variations in receptor number and affinity in the literature, and methods for quantitative characterization of parameters.

SUBMITTER: Kausthubh Ramachandran

PROVIDER: BIOMD0000000985 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000985?filename=Gex-Fabry1984-biopax2.owl	Owl
	BIOMD0000000985?filename=Gex-Fabry1984-biopax3.owl	Owl
	BIOMD0000000985?filename=Gex-Fabry1984-matlab.m	Other
	BIOMD0000000985?filename=Gex-Fabry1984-octave.m	Other
	BIOMD0000000985?filename=Gex-Fabry1984.cps	Other

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Publications

Receptor-mediated endocytosis: a model and its implications for experimental analysis.

Gex-Fabry M M DeLisi C C

The American journal of physiology 19841101 5 Pt 2

We present a mathematical model for analyzing, simulating, and quantitating the dynamic and steady-state characteristics of receptor-mediated endocytosis. The basic processes considered by the model are ligand-receptor binding, diffusion of receptors and ligand-receptor complexes in the plane of the membrane toward and away from coated pits, binding of ligand-receptor complexes to coated pit proteins, endocytosis of coated pit contents, degradation of ligand, and recycling of undegraded receptor ...[more]

PMID: 6149699

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Project description:Sivakumar2011 - EGF Receptor Signaling Pathway EGFR belongs to the human epidermal receptor (HER) family of receptor tyrosine kinases, which consists of four closely related receptors (EGFR (HER1, erbB1), HER2 (neu, erbB2), HER3 (erbB3), and HER4 (erbB4)) that mediate cellular signaling pathways involved in growth and proliferation in response to the binding of a variety of growth factor ligands. There are currently six known endogenous ligands for EGFR: EGF, transforming growth factor- (TGF-), amphiregulin, betacellulin, heparin-binding EGF (HB-EGF), and epiregulin.Upon ligand binding, the EGFR forms homo- or heterodimeric complexes (usually with HER2), which leads to activation of the receptor tyrosine kinase, via autophosphorylation. References: The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. EGF receptor signaling: putting a new spin on eye development. Epidermal growth factor receptor: a promising target in solid tumours. This model is described in the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. Omics: a Journal of Integrative Biology. 2011; 15(10):729-737 Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs. This model is hosted on BioModels Database and identified by: BIOMD0000000394. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.