Signal transduction intracellular messengers

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

In addition to its role as a bone component, calcium functions as a signaling substance. Ca "" ions act as second messengers in signal transduction pathways (see p. 386), they trigger exocytosis (see p. 228) and muscle contraction (see p. 334), and they are indispensable as cofactors in blood coagulation (see p. 290). Many enzymes also require Ca "" for their activity. The intracellular and extracellular concentrations of Ca "" are strictly regulated in order to make these functions possible (see B, C, and p.388). 

Components of the intracellular signal transduction are proteins and small molecule messengers (fig. 3.3). An incoming signal is passed on from the receptor to down-... 

The intracellular activation of enzymes in a signaling chain can lead to the formation of diffusible chemical signaling molecules in the cell. These intracellular signaling molecules are also termed second messengers. The second messenger molecules activate and recruit cognate enzymes for the further signal transduction. 

The regulation of the subtypes I, III and VIII by Ca /cahnodulin stands out. All three subtypes are stimulated by Ca, although in different concentration regions. Ca is, as discussed in more detail in Chapter 6, a central intracellular messenger substance, and an increase in the Ca concentration is observed on activation of different signal transduction processes. 

The intracellular messengers are diffusible signal molecules and reach their target proteins mostly by diffusion. Close spatial proximity of the signal components, as achieved for transmembrane receptors and their effector proteins with the help of membrane anchoring or with specific protein-protein modules (see Chapter 5, Chapter 8), is not necessarily required for this type of signal transduction. 

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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