Measurement of the formation of complexes in tyrosine kinase-mediated signal transduction.
Isothermal titration calorimetry (ITC) provides highly complementary data to high-resolution structural detail. An overview of the methodology of the technique is provided. Ultimately, the correlation of the thermodynamic parameters determined by ITC with structural perturbation observed on going from the free to the bound state should be possible at an atomic level. Currently, thermodynamic data provide some insight as to potential changes occurring on complex formation. Here, this is demonstrated in the context of in vitro quantification of intracellular tyrosine kinase-mediated signal transduction and the issue of specificity of the important interactions. The apparent lack of specificity in the interactions of domains of proteins involved in early signalling from membrane-bound receptors is demonstrated using data from ITC.
Ladbury
John E
JE
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, England. j.ladbury@biochem.ucl.ac.uk
D000818:Animals; D002151:Calorimetry / Q000379:methods*; D019277:Entropy; D006358:Hot Temperature; D007700:Kinetics; D008954:Models, Biological; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013696:Temperature; D013816:Thermodynamics; D018909:src Homology Domains
D010455:Peptides; D011505:Protein-Tyrosine Kinases