User:J. C. Martinez-Garcia/Notebook/HMS Activities/2008/10/25
|Desensitization||Main project page|
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The meaning of the term
From the paper J.L. Martiel, A. Goldbeter (1987): A model based on receptor desensitization for cyclic AMP signaling in Dictyostelium cells. Byophys. J, Vol. 52, pp. 807-828.: The phenomenon of desensitization (which classical model is given in the paper: Katz, B. and S. Thesleff (957): A study of "desensitization" produced by acetylcholine at the motor end-plate. J. Phsysiol. (Lond). 138: 63:80) accounts for a decrease in responsiveness upon prolonged stimulation, and is explained by the transition of the receptor into a high-affinity state les or not coupled to the pshysiological response. Such a mechanism is exemplified by the acetyl-choline receptor for which multiple conformational states possesing different affinities for the ligand have indeed been observed. The receptor states may, however, differ not only by their conformation but also by their degree of covalent modification. A large number of receptors that play a role in the sensing of external stimuli are known to be covalently modified. Thus phosphorylation of the β-adrenergic receptor in turkey erythrocytes is associated with a decrease in adenylate cyclase activity. In bacteria, stimulation by chemical attractants causes to constant stimuli is brought about by methylation of the chemoreceptors.
I reviewed some information on the way the Zstk drug works and I found the original paper describing it: S. Yaguchi et al (2006): Antitumor Activity of ZSTK474, a New Phosphatidylinosol 3-Kinase Inhibitor. Journal of the National Cancer Institute, Vol. 98, No. 8 (which is here Media:zstk_effect.pdf). The drug works binding to the protein PI3K, and as a consequence Pi3K is inhibited and so PI3K can not phosphorylates AKT and the glycogen synthasa kinase 3β.
Working with a reduced model
I think that is is better to work with a model describing the observed phenomenon and not necessarily the biological phenomena which underlies the observed results. The model must be obtained from scratch using the cartoon given by the following figure: