Reaction Signalling pathway

Mg2+ Glycolytic pathway (enolase) All kinases and NTP reactions" Signalling (transcription factors) DNA/RNA structures Light capture... 

The next key point is to realize that each enzyme in the pathway exists in both active and inactive forms. cAMP initiates a cascade of reactions by activating protein kinase A (PK-A)," the active form of which activates the next enzyme in the sequence, and so on. At the end of the day, glycogen phosphorylase is activated and glucose or ATP is produced. This signaling pathway is a marvelous amplification system. A few molecules of glucagon or adrenaline may induce formation of many molecules of cAMP, which may activate many of PK-A, and so on. The catalytic power of enzymes is magnified in cascades of this sort. 

Intercellular signaling influences nearly every physiological reaction. It ensures that all cells of a particular type receive and transform a signal. In this manner, cells of the same type react synchronously to a signal. A further function of signaling pathways is the coordination of metabolite fluxes between cells of various tissues. 

The switch for the activation of an intracellular signaling pathway is in most cases an increase in the concentration of the freely circulating hormone. This leads to an increase in the concentration of the hormone-receptor complex, which results in an increased activation of subsequent reactions in the cell. The concentration of the circulating hormone is thus the main regulatory parameter in cellular conummication. The relation between hormone concentration, binding of the hormone to the receptor, and subsequent reaction in the cell is illustrated in fig. 3.7 for the case of adrenaline and the P-adrenergic receptor. 

Fig. 3.8. Variability of receptor systems and signal pathways, a) For one receptor of a given binding specificity (binding to hormone H) there can be different snbtypes in the same ceU (Rl, R2) or in other cell types (Rl )- b) The hormone H can induce different reactions (X, X ) upon binding the different receptor types (Rl, R2). The receptor types Rl and R2 can be found simultaneous in one cell, c) the binding of two different hormones (H, H ) to different receptors (Rl , R3) can induce the same intracellular reaction. The characteristics a) and b) contribute to a high degree to the diversity and variability of hormonal signal transduction. Point c) illustrates the principle that important cellular metabolites or reactions can be controlled by different signal transduction pathways.

The highly variable nature of signaling pathways is also expressed by the fact that different receptors and signaling pathways can induce the same biochemical reaction in a cell. This is exemplified by the release of Ca, which can be regulated via different signaling pathways (see chapters 5-7). 

Signal pathways commonly amplify the initial signal received by the receptor during the course of the signal transduction (fig. 3.9). In many cases only a few molecules of a hormone are sufficient to initiate an enzymatic reaction in a cell, in which many substrate molecules are turned over. 

Fig. 5.5. General functions of transmembrane receptors. Extracellular signals convert the transmembrane receptor from the inactive form R to the active form R. The activated receptor transmits the signal to effector proteins next in the reaction sequence. Important effector reactions are the activation of heterotrimeric G-proteins, of protein tyrosine kinases and of protein tyrosine phosphatases. The tyrosine kinases and tyrosine phosphatases may be an intrinsic part of the receptor or they may be associated with the receptor. The activated receptor may also include adaptor proteins in the signaling pathway or it may induce opening of ion channels.

Phospholipase C, which occurs in different subtypes in the cell, is a key enzyme of phosphatide inositol metabohsm (for cleavage specificity, see Fig. 5.24). Two central signaling pathways regulate phosphohpase C activity of the cell in a positive way (Fig. 6.4). Phospholipases of type CP (PL-CP) are activated by G-proteins and are thus linked into signal pathways starting from G-protein-coupled receptors. Phosphohpases of type Y (PL-Cy), in contrast, are activated by transmembrane receptors with intrinsic or associated tyrosine kinase activity (see Chapter 8, Chapter 10). The nature of the extracellular stimuli activated by the two major reaction pathways is very diverse (see Fig 6.4), which is why the phosphohpase C activity of the cell is subject to multiple regulation. 

Fig. 9.1. The Ras protein as a central switching station of signaling pathways. A main pathway for Ras activation is via receptor tyrosine kinases, which pass the signal on via adaptor proteins and guanine nucleotide exchange factors to the Ras protein. Activation ofRas protein can also be initiated via G-protein-coupled receptors and via transmembrane receptors with associated tyrosine kinase activity. The membrane association of the Ras protein (see Fig. 9.6) is not shown for clarity. In addition, not aU signahng pathways that contribute to activation of the Ras protein are shown, nor are all effector reactions. Py omplex of the heterotrimeric G proteins GAP GTPase activating protein GEF guanine nucleotide exchange factor.

Intracellular signal conduction takes place predominantly by two pathways starting from activated transmembrane receptors. In one pathway, activation of transmem -brane receptors initiates formation of diffusible messenger substances that bind effector proteins and activate these for further signal transduction. In this signaling pathway, signals may be carried as far as the cell nucleus and temporally and spatially variable reactions may be triggered. 

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