Enhancer receptors

Upon activation by CXCLl2, CXCR4 is quickly phosphorylated and internalized. Several residues in its C-terminus tail have been identified as potential phosphorylation sites by truncation and mutagenesis studies as reviewed in Busillo and Benovic (2007). Removal of 45 amino acid residues from the C-terminal of CXCR4 led to elimination of CXCL12-induced phoshorylation, enhanced receptor activity... 

Heterologous desensitisation refers to the desensitisation of the response to one agonist by the application of a different agonist. For example, desensitisation of a response to adrenaline by application of 5-HT is mediated by protein kinase A or protein kinase C because these kinases can phosphorylate receptors which are not occupied by agonist. Phosphorylation disrupts the receptor-G-protein interaction and induces the binding of specific proteins, arrestins which enhance receptors internalisation via clathrin-coated pits. Thus desensitisation of G-protein-coupled receptors results in a decrease in the number of functional receptors on the cell surface. 

Wagner E, Zatloukal K, Cotten M, Kirlappos H, Mechtler K, Curiel DT, Bimstiel ML (1992) Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-... 

In contrast to the enhanced receptor expression that occurs during activation and priming, the expression of some receptors actually decreases during this process. This is particularly evident with receptors such as CD16 (the low-affinity receptor for IgG) and the ligand that binds monoclonal antibody 31D8 (a surface molecule of undefined nature whose expression is closely linked to fMet-Leu-Phe responsiveness). These molecules are GPI-linked and are shed from the cell surface during activation (see Fig. 3.10). 

The most parsimonious model for upregulation that acconunodates current information suggests that nicotine binding to inunature subnnits enhances receptor assembly by provoking quaternary structure rearrangements (that might resnlt in altered subunit stoichiometry), leading to accelerated maturation of nAChRs and a net... 

If the same endocytic LCM-uptake mechanism(s) which has been observed and analyzed in detail with C6 and 9L tumor cells in culture (see Section 13.1) were also operative in vivo, it would indicate that a sizable portion of intravenously injected LCM that bypasses the reticuloendothelial system will then become endo-cytosed directly by tumor cells (ref. 531). The actual endocytic pathways that are likely to be involved in LCM uptake by tumors are not known, at the present time, due to the lack of any detailed receptor-binding studies with LCM to date. However, a few reasonable candidates for such endocytic pathways emerge upon reviewing parts of an extensive research literature describing significantly enhanced, receptor-mediated endocytosis in many different cancerous cells and solid tumors (see below). 

The identification of point mutations that enhance receptor basal activity is a strategy used to better understand the differences between... 

More than half of the peptide hormones undergo postsynthetic modification to form a carboxy terminal amide, which is essential for biological activity. One function of this amidation is to render the peptides more hydrophobic and enhance receptor binding. The amide group is derived from a glycine residue that is to the carboxyl side of the amino acid which will become the amidated terminal of the mature peptide. 

Enhanced Receptor Effect in Various Lanthanide/Analyte Systems. 

Fig. 8 Enhanced receptor effect on analyte binding affinity. Upon chelation, the electronegative ancillary ligand causes a polarization of the Ln + ion, inducing an increased positive charge at the binding site. This anisotropy results in an increased binding affinity for the anionic analyte. Limit of detection (LOD) values shown are for the Tb/D02A/ dipicolinate system.

Wagner, E., Zatloukal, K., Cotten, M., Kirlappos, H., Mechtler, K., Curiel, D.T., and Bimstiel, M.L. (1992). Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc. Natl. Acad Sci. USA 89, 6099 6103. 

Phase I metabolism Phase II metabolism Enzyme induction Enzyme inhibition OS enhancement Receptor interaction Endocrine disruption Immunosuppression Immunostimulation... 

Because we were unable to find, using [3H]-(-)-BPAP, direct evidence for specific enhancer receptors, we tried to approach the problem from another angle. In the rat brain, using a classic pharmacological method, we found convincing indirect evidence for (-)-BPAP-sensitive enhancer receptors in the mesencephalon (Knoll et al. 2002a). 

The obvious difference already established between the binding of (-)-deprenyl and (-)-BPAP (Knoll et al. 1999) argues for the existence of various types of enhancer receptors. Remarkably, Borowsky et al. (2001) found that more than one memb er of the newly identified family of mammalian G-protein-coupled receptors was activated by PEA and tryptamine. 

Not only the real nature of the specific mesencephalic enhancer receptors but also the endogenous ligands to these receptors remain unresolved. The high potency of (-)-BPAP in comparison to the already identified natural enhancer substances, PEA and tryptamine, is remarkable. This difference gives justification for the search for much more potent natural enhancer substances than PEA and tryptamine. 

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