title: Dynamics of receptor and protein transducer homodimerisation.
abstract: BACKGROUND
  Signalling pathways are complex systems in which not only simple monomeric molecules interact, but also more complex structures that include constitutive or induced protein assemblies. In particular, the hetero-and homo-dimerisation of proteins is a commonly encountered motif in signalling pathways. Several authors have suggested in recent times that dimerisation relates to a series of physical and biological outcomes used by the cell in the regulation of signal transduction.
  
  
  RESULTS
  In this paper we investigate the role of homodimerisation in receptor-protein transducer interactions. Towards this end, mathematical modelling is used to analyse the features of such kind of interactions and to predict the behaviour of the system under different experimental conditions. A kinetic model in which the interaction between homodimers provokes a dual mechanism of activation (single and double protein transducer activation at the same time) is proposed. In addition, we analyse under which conditions the use of a power-law representation for the system is useful. Furthermore, we investigate the dynamical consequences of this dual mechanism and compare the performance of the system in different simulated experimental conditions.
  
  
  CONCLUSIONS
  The analysis of our mathematical model suggests that in receptor-protein interacting systems with dual mechanism there may be a shift between double and single activation in a way that intense double protein transducer activation could initiate and dominate the signal in the short term (getting a fast intense signal), while single protein activation could control the system in the medium and long term (when input signal is weaker and decreases slowly). Our investigation suggests that homodimerisation and oligomerisation are mechanisms used to enhance and regulate the dynamic properties of the initial steps in signalling pathways.
authors.affiliation: University of Rostock, Rostock, Germany. jv030@informatik.uni-rostock.de
authors.forename: Julio
authors.initials: J
authors.lastname: Vera
authors.forename: Thomas
authors.initials: T
authors.lastname: Millat
authors.forename: Walter
authors.initials: W
authors.lastname: Kolch
authors.forename: Olaf
authors.initials: O
authors.lastname: Wolkenhauer
mesh_terms: D003198:Computer Simulation; D007700:Kinetics; D008954:Models, Biological; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011506:Proteins