Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding
| dc.creator | Gopalakrishnan, Manoj | |
| dc.creator | Forsten-Williams, Kimberly | |
| dc.creator | Tauber, Uwe C. | |
| dc.date | 2003-08-18 | |
| dc.date.accessioned | 2026-07-07T02:52:57Z | |
| dc.date.available | 2026-07-07T02:52:57Z | |
| dc.description | 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. | |
| dc.description | 32 pages, 9 figures included, submitted to J. Theor. Biol | |
| dc.identifier | https://arxiv.org/abs/cond-mat/0308348 | |
| dc.identifier | http://arxiv.org/abs/cond-mat/0308348 | |
| dc.identifier | J. Theor. Biol. 227(2) 239-251 (2004) | |
| dc.identifier.uri | http://salesiana.dossiersoluciones.com/handle/123456789/22034 | |
| dc.subject | Statistical Mechanics | |
| dc.subject | Soft Condensed Matter | |
| dc.subject | Biological Physics | |
| dc.subject | Subcellular Processes | |
| dc.title | Ligand-induced Coupling versus Receptor Pre-association: Cellular automaton simulations of FGF-2 binding | |
| dc.type | text |