Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding

Details Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding

2003-08-18

arxiv.org/abs/cond-mat/0308348v1

J. Theor. Biol. 227(2) 239-251 (2004)

Physics

Condensed Matter

Statistical Mechanics

32 pages, 9 figures included, submitted to J. Theor. Biol

Scientific paper

The binding of basic fibroblast growth factor (FGF-2) to its cell surface receptor (CSR) and subsequent signal transduction is known to be enhanced by Heparan Sulfate Proteoglycans (HSPGs). HSPGs bind FGF-2 with low affinity and likely impact CSR-mediated signaling via stabilization of FGF-2-CSR complexes via association with both the ligand and the receptor. What is unknown is whether HSPG associates with CSR in the absence of FGF-2. In this paper, we determine conditions by which pre-association would impact CSR-FGF-2-HSPG triad formation assuming diffusion-limited surface reactions. Using mean-field rate equations, we show that (i) when [HSPG] is much higher than [CSR], the presence of pre-formed complexes does not affect the steady state of FGF-2 binding, and (ii) when the concentrations are comparable, the presence of pre-formed complexes substantially increases the steady state concentration of FGF-2 bound to CSR. These findings are supported by explicit cellular automaton simulations, which justify the mean-field treatment. We discuss the advantages of such a two-receptor system compared to a single receptor model, when the parameters are comparable. Further, we speculate that the observed high concentration of HSPG in intact cells ([HSPG] ~ 100[CSR]) provides a way to ensure that the binding levels of FGF-2 to its signaling receptor remains high, irrespective of the presence of pre-formed CSR-HSPG complexes on the cell surface, while allowing the cell to finely tune the response to FGF-2 via down-regulation of the signaling receptor.

Affiliated with

Also associated with

No associations

Rating

Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.

If you have personal experience with Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFWR-SCP-O-206837