Receptor in signal transduction

Heldin, C. H. (1995). Dimerization of cell surface receptors in signal transduction. Cell 80 213-223. 

Sugawara H, Kurosaki M, Takata M, Kurosaki T 1997 Genetic evidence for involvement of type 1, type 2 and type 3 inositol 1,4,5-trisphosphate receptors in signal transduction through the B-cell antigen receptor. EMBO J 16 3078-3088... 

Bos CL, Richel DJ, Ritsema T, Peppelenbosch MP, Versteeg HH. Prostanoids and prostanoid receptors in signal transduction. Int. J. Biochem. Cell. Biol. 2004 36 1187-1205. 

The cytoplasmic tail. This domain of the LDL receptor constitutes a short stretch of 50 amino acid residues involved in the targeting of LDL receptors to coated pits. Naturally occurring mutations and site-specific mutagenesis (M.A. Lehrman, 1987) have identified an internalization signal , Asn-Pro-Xxx-Tyr (NPxY in Fig. 3, where Xxx denotes any amino acid). Recently, the cytoplasmic domains of the LDL receptor and structural relatives have come into new focus, since they hold the key to the involvement of these receptors in signal transduction (Sections 5.2., 5.3., and 6.1). For further details on these aspects, see Ref. [6]. 

Genetic models reveal new roles for apoERl and VLDL receptor in signal transduction... 

In this chapter we describe some examples of structures of membrane-bound proteins known to high resolution, and outline how the elucidation of these structures has contributed to understanding the specific function of these proteins, as well as some general principles for the construction of membrane-bound proteins. In Chapter 13 we describe some examples of the domain organization of receptor families and their associated proteins involved in signal transduction through the membrane. 

Pharmocodynamic tolerance develops in response to continued application of drugs, by mechanisms that include reversible cellular adaptation processes, such as receptor desensitization, internalization and downregu-lation as well as changes in the activity and levels of other components of the receptor s signal transduction pathways. 

Desensitization describes the rapid signal attenuation in response to stimulation of cells by receptor agonists. Changes in the coupling efficiency of receptors to signal transduction pathways and receptor internalization can account for desensitization and the development of pharmacodynamic tolerance. 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

MacGlashan D Jr IgE receptor and signal transduction in mast cells and basophils. Curr Opin Immunol 2008 20 717-723. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Brink CB, Harvey BH, Bodenstein J, Venter DP, Oliver DW. Recent advances in drug action and therapeutics relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology. Br J Clin Pharmacol 2004 57(4) 373-387. 

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