Signal transduction steps

Figure 4. A flow diagram showing the signal transduction steps that couple the muscarinic receptor to the mKATp in a rabbit cardiomyocytc. Note the complexity of the pathway. See text for a detailed explanation.

The initial observation that FPR accumulate in the Triton X-100-insoluble fraction of neutrophils upon desensitization led to a more detailed study of the cellular structures that might be implicated in the regulation of receptor function. The signal transduction steps that involve the receptor protein as well as the crucial desensitization events appear to take place in the plasma membrane because desensitization does occur at 15°C, a temperatur that inhibits internalization of receptors [41]. Therefore, a potential interaction of receptors with cytoskeletal proteins on the level of the plasma membrane was investigated. 

Numerous studies have shown that EGF binding to EGFR triggers receptor dimerization. This is considered a crucial step in intracellular signal transduction [98]. Inspired by this mechanism, we designed EGF chimeric proteins that spontaneously dimerized (dEGF-His). These dimers were terminally anchored to the substrate. We expected that these preformed dimeric EGF structures would facilitate the formation of EGF-EGFR dimer complexes more efficiently than monomeric EGF structures. 

This method has been applied in the enantioselective synthesis of d-erythro-sphingosine and phytosphingosine. Sphingosine became an important substance for studying signal transduction since the discovery of protein kinase C inhibition by this compound.48 Many efforts have been made to synthesize sphingosine and its derivatives.49 Kobayashi et al. reported another route to this type of compound in which a Lewis acid-catalyzed asymmetric aldol reaction was a key step. 

The Ras signal transduction cascade is of extreme physiological importance. It is central to the regulation of cell growth and differentiation, and false regulation of this signal pathway can be one of the critical steps leading to cell transformation.151 A... 

U. Weimar. Gas Sensing with Tin Oxide Elementary Steps and Signal Transduction, HabU-itation thesis. University of Tubingen, Germany (2001). 

Over the last decade, a substantial amoimt of information about properties and spatial structures of different representatives of the TGF- superfamily, both free and in complexes with ectodomains of their transmembrane receptors, have been accumulated. Consequently, a number of important steps towards understanding initiation and actuation of TGF-b signahng, as well as the biological response to the signal transduction and interplay with other signaling pathways have been made [2,12,18,46-50]. 

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