Receptor interactions directly

White, J. H., Mclllhinney, R. A., Wise, A., Ciruela, F., Chan, W. Y., Emson, P. C., et al. (2000) The GABAb receptor interacts directly with the related transcription factors CREB2 and ATFx. Proc. Natl. Acad. Sci. USA 97,13967-13972. 

Sugai M, Saito M, Sukegawa I, Katsushima Y, Kinouchi Y, Nakahata N, Shimosegawa T, Yanagisawa T, Sukegawa J (2003) PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH terminus. Biochem Biophys Res Commun 311 24-31... 

Fig. 4.10. Principle of signal transduction by steroid hormone receptors. The steroid hormone receptors in the cytosol are found in the form of an inactive complex with the heat shock proteins Hsp90 and Hsp56 and with protein p23. The binding of the hormone activates the receptor so that it can be transported into the nucleus where it binds to its cognate HRE. It remains unclear in which form the receptor is transported into the nucleus, and to which extent the associated proteins are involved in the transport. One mechanism of activation of transcription initiation involves activation of a histone acetylase and remodehng of chromatin. Furthermore, the receptors interact directly or indirectly with components of the RNA polymerase II holoenzyme (e.g. SUGl).

Although each class of glutamate receptor interacts directly with a different set of cytoplasmic proteins, they all seem to act as a membrane node from which emanates a network of specific protein-protein interactions into the cell interior. These networks of proteins may overlap and converge at some points, such as on the Shank family of proteins. The functional consequences of these biochemical interactions need to be determined. 

Direct quantitation of receptor concentrations and dmg—receptor interactions is possible by a variety of techniques, including fluorescence, nmr, and radioligand binding. The last is particularly versatile and has been appHed both to sophisticated receptor quantitation and to dmg screening and discovery protocols (50,51). The use of high specific activity, frequendy pH]- or p lj-labeled, dmgs bound to cmde or purified cellular materials, to whole cells, or to tissue shces, permits the determination not only of dmg—receptor saturation curves, but also of the receptor number, dmg affinity, and association and dissociation kinetics either direcdy or by competition. Complete theoretical and experimental details are available (50,51). 

The hypothetical enantiophore queries are constructed from the CSP receptor interaction sites as listed above. They are defined in terms of geometric objects (points, lines, planes, centroids, normal vectors) and constraints (distances, angles, dihedral angles, exclusion sphere) which are directly inferred from projected CSP receptor-site points. For instance, the enantiophore in Fig. 4-7 contains three point attachments obtained by ... 

Mathematical models are the link between what is observed experimentally and what is thought to occur at the molecular level. In physical sciences, such as chemistry, there is a direct correspondence between the experimental observation and the molecular world (i.e., a nuclear magnetic resonance spectrum directly reflects the interaction of hydrogen atoms on a molecule). In pharmacology the observations are much more indirect, leaving a much wider gap between the physical chemistry involved in drug-receptor interaction and what the cell does in response to those interactions (through the cellular veil ). Hence, models become uniquely important. 

In many cases where a receptor consists of multiple polypeptides, one of those polypeptides (which will be unique to that receptor) will interact directly with the ligand. The additional polypeptide(s), responsible for initiation of signal transduction, may be shared by a number of receptors (Figure 8.1). 

The a chain binds IL-2 with low affinity, with binding being characterized by high subsequent association-disassociation rates. The y subunit does not interact directly with IL-2. It is sometimes known as yc (common), as it also appears to be a constituent of the IL-4, -7, -9, -13 and -15 receptors. 

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