Intracellular signaling pathways, activation

Segal, R.A. and Greenberg, M.E. (1996) Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 19 463-489. 

Figure 14-9 summarizes the Intracellular signaling pathways activated when the EpoR binds erythropoietin. Stimulation of other cytokine receptors by their specific ligands activates similar pathways. All these pathways eventually lead to activation of transcription factors, causing an Increase or decrease in expression of particular target genes. Flere we focus on the JAK STATpathway the other pathways are discussed in later sections. 

Fig. 6.4. hlypothetical model of the intracellular signaling pathways activated by cannabinoid CBj receptors. Stimulation of these receptors causes activation of potassium channels and inhibition of calcium channels and adenylate cyclase activity. The diagram combines results obtained in various heterologous expression systems, as described in refs. 9-12. 

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

Blanpain C, Wittamer V, Vanderwinden JM, et al. Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. J Biol Chem 2001 276(26) 23795-23804. 

Three phases of receptor-mediated signaling can be identified 178 Four distinct molecular mechanisms that link agonist occupancy of cell-surface receptors to functional responses have been identified 178 Cross-talk can occur between intracellular signaling pathways 179 Signaling molecules can activate gene transcription 181 Nitric oxide acts as an intercellular signaling molecule in the central nervous system 181... 

Ligand-activated intracellular signaling pathways induce the transcription of ERGs that encode for four categories of cell proteins (1) transcription factors,... 

Parathyroid hormone (PTH) regulates calcium levels in blood and bone remodeling. The activation domain of that 84-amino acid polypeptide locates around the N-terminal (1-34 amino acids). Parathyroid hormone receptor is a typical G-protein coupled receptor, which is coupled to both adenyl cyclase/cAMP and PLCy/IP3/cytosolic Ca2+ intracellular signaling pathways. In order to identify the structural elements involved in the peptide hormone binding and signal initiation, Chorev et al. employed a photoaffinity scanning approach. The N-terminal amino acids were successively deleted or modified and the new N-terminus was replaced for photoreactive Bpa. The most active peptide ana-... 

There are a variety of structural classes of compounds that are active against each phosphodiesterase, and evidence suggests that selective inhibitors of PDEs can be identified. The structural diversity of PDE inhibitors provides a multitude of opportunities for development of compounds with drug-like properties. Furthermore, phosphodiesterase inhibition, which avoids direct interaction of a compound with a cell surface or nuclear receptor, may circumvent some of the target selectivity issues that can complicate receptor-based therapeutic approaches. As noted above, the specific subcellular distribution of phosphodiesterase enzymes is a key feature of their ability to modulate intracellular signaling pathways. This localization of the enzyme may minimize non-specific target... 

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