Signal transduction fundamentals

It is important to appreciate that this principle of coupling-in-series underlies all biochemical pathways or processes, e.g. glycolysis, generation of ATP in the mitochondrion, protein synthesis from amino acids or a signal transduction pathway. Indeed, despite the fundamental importance of signalling pathways in biochemistry, a thermodynamic analysis of such a pathway has never been done, but the principles outlined above must apply even to signalling pathways. 

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

Considerable effort over the years has been expended to identify specific neurotransmitter systems that might mediate the therapeutic action of lithium in the treatment of patients with bipolar disorder. As we critically review the evidence from these studies, it will be evident that lithium can affect a variety of neurotransmitter systems, but these effects may be secondary to more fundamental modulation of signal transduction responsible for regulating the balance of signaling in critical regions of the brain. 

The detection of light, smells, and tastes (vision, olfaction, and gustation, respectively) in animals is accomplished by specialized sensory neurons that use signal-transduction mechanisms fundamentally similar to those that detect hormones, neurotransmitters, and growth... 

In all systems studied thus far, olfactory-stimulated signal transduction is mediated by G-protein-coupled receptor (GPCR) pathways involving the synthesis of second messengers such as cyclic AMP (cAMP) and/or inositol 1,4,5-triphosphate (IP3) (Boekhoff et al., 1994 Reed, 1992). Moreover, several proteins that are involved in fundamental aspects of olfactory signal transduction have... 

Signal transduction is as fundamental a feature of life as metabolism and self-replication. 

Receptor pre-assembly has also been described for other receptor families and appears to be a fundamental principle for the signal transduction of oligomeric receptors. For example, the insulin receptor is a... 

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