Signal transduction modeling

Signal Transduction Models Chemical/Physical Foundations... 

Signal Transduction Model The pharmacological effects of drugs may be mediated by a time-dependent signal transduction process, which involves multiple steps. Sun and Jusko proposed a signal transduction model to account for the delayed effect of pharmacodynamic responses. This model has been used to characterize the parasympathomimetic activity of scopolamine and atropine in rats. ... 

Implementation of the general signal transduction model requires a search for an optimal number of transit compartments (N), which usually is the fewest that... 

FIGURE 23.8 Simulated response profiles (solid lines) for the signal transduction model shown in Figure 23.7. The E function is defined by Eq. (23.1) and the response is set equal to the time course of the M3 compartment. Parameter values are ka = 0.3 E° = 0 unit, T= 5.Oh, Emax = 100 units, 7= 1.0, and EC50 = 10 units. 

Calculation of Conformational Free Energies for a Model of a Bilobal Enzyme Protein kinases catalyze the transfer of phosphate from adenosine triphosphate (ATP) to protein substrates and are regulatory elements of most known pathways of signal transduction. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Hare, P.D., Cress, W.A., and Van Staden, J., Proline synthesis and degradation a model system for elucidating stress-related signal transduction, J. Exp. Bot, 50, 413,... 

Fig. 12. Tentative model of the signal transduction chain that links the perception of pectic fragments to defense responses in carrot cells. Abbreviations apy, heterotrimeric G protein CaM, calmodulin 4CL, 4-coumarate-CoA ligase CTX, cholera toxin FC, fusicoccine GDP-P-S and GTP-y-S, guanosine 5 -0-(2-thiodiphosphate) and guanosine 5 -0-(3-thiotriphosphate) IP3, 1,4,5-inositol trisphosphate PAL, phenylalanine ammonia-lyase PLC, phospholipase C PR, pathogenesis related PTX, pertussis toxin Rc, receptor SP, staurosporine. Activation and inhibition are symbolized by + and -respectively.

This linear scheme of signal transduction (Fig. 12) from hypothetical membrane receptors to [Ca " ] and IP3 increases, calcium-calmodulin interaction, kinases activation and gene transcription is clearly an oversimplification of the reality several receptors must exist that are connected to different transduction cascades that activate a series of defense genes. Cross-talking between the pathways further complicates the picture. However, this represents a starting model on which to elaborate more refined hypotheses. 

A study of the molecular descriptions provided by geneticists and molecular biologists reveals at least three different levels. The first can be illustrated by the schematic models of signal-transduction pathways. In such models, the precise shape of the different proteins, their atomic composition, is of no importance. Sometimes, only the name of the protein is given. What is important is the place of these proteins in the pathways, how they receive upstream signals and transfer them to downstream molecular components. 

Wang JF, Li PP et al. Signal transduction abnormalities in bipolar disorder in Bipolar Disorder Biological Models and their Clinical Application (Joffe RT and Young LT, Eds), Marcel Dekker, New York 1997, pp 41-79. 

Drug-receptor interactions Dose-response relationships Molecular modeLs of receptors and signal transduction mechanisms Biotr an s fo r m ati on Ph ar macokine t ios Ph armacody namics... 

Adenylyl cyclase in learning and memory. The cAMP-signal transduction cascade has been demonstrated to play a role critical to the formation of long-term memory in both cellular models and in animals. The specific adenylyl cyclases involved are being identified by current research. In AC1 mutant mice there is a partial disruption of long-term potentiation (LTP), a cellular model of... 

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