The role of signaling pathways

In this chapter we discuss the free-radical-induced modification of the various cellular components and the mechanisms by which oxidative stress leads to carcinogenesis. The role of signaling pathways in regulating cell proliferation and in promoting carcinogenesis is also discussed. 

Alternately, evidence also exists that Coronin lA s role may be to control calcium dynamics after bacterial infection. Macrophages from mice lacking Coronin lA do not display the persistent increase in calcium levels that are normally displayed after infection. This consequently prevents the activation of signaling pathways via proteins such as the calcium-sensitive phosphatase Calcineurin. While no alterations in actin dependent processes have been detected in Coronin lA null macrophages, the effects may be linked to more subtle effects on actin that affect the known relationship between cytoskeletal dynamics and calcium trafficking. Dramatic effects on actin-dependent processes may also be masked by the presence of functionally redundant Coronin isoforms in this cell type. 

One should note overall, that while some of these suggested mechanisms may in the future prove to have a role in the control of smooth muscle contraction, in chemically skinned preparations maximum force development follows activation by the MLCK active subunit in extremely low Ca " ion concentrations. The conclusion can hardly be avoided that phosphorylation alone is sufficient for activation, and if another mechanism is involved, it is not necessary for the initial genesis of force. If such mechanisms are operative, then they might be expected to run in parallel or consequent to myosin phosphorylation. A possible example of this category of effect is that a GTP-dependent process (G-protein) shifts the force vs. Ca ion concentration relationship to lower Ca ion concentrations. This kind of mechanism calls attention to the divergence of signals along the intracellular control pathways. 

Figure 21.3 Modeling and simulation in the general context of the study of xenobiot-ics. The network of signals and regulatory pathways, sources of variability, and multistep regulation that are involved in this problem is shown together with its main components. It is important to realize how between-subject and between-event variation must be addressed in a model of the system that is not purely structural, but also statistical. The power of model-based data analysis is to elucidate the (main) subsystems and their putative role in overall regulation, at a variety of life stages, species, and functional (cell to organismal) levels. Images have been selected for illustrative purposes only. See color plate.

Root flavonoids that may act as signals for the initiation and development of endomycorrhizal and ectomycorrhizal symbio.ses have been identified (see Chap. 7). Metabolites of the phenylpropanoid pathways apparently act as signaling molecules in endo- and ectomycorrhizal interactions (14). The role of flavonoids is still controversial, but a variety of flavanones, flavones, and isoflavones... 

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