Receptors signaling

Sigma (s-) receptors Signal flares Signaling smokes Signal modulators Signal processing... 

Felder, C. C. (1995). Muscarinic acetylcholine receptors . Signal transduction through multiple effectors. FASEB j. 9, 619-625. 

Cellular amplification of receptor signals occurs through a succession of saturable biochemical reactions. Different... 

Receptor signaling can be modulated to a reduced (but not to basal) level. 

Effect is linked to receptor signal. Thus, complex physiological patterns may be preserved. 

The first case to consider is where the modulator affects only the affinity of the receptor for the agonist but does not alter receptor signaling. Under these circumstances, ,= 1 and Equation 7.3 reduces to... 

The receptor can bind both the probe (agonist, radioligand, [A]) and allosteric modulator ([B]). The agonist (7.11) bound receptor signal through the normal operational model ([AR] complex interacting with cellular stimulus-response machinery with association constant Ke) and in a possibly different manner when the allosteric modulator is bound (complex [ABR] interacting with cell with... 

Thus, the non-zero , term reduces the effect of a on the pA2 estimate. It can be seen that when receptor signaling is blocked by the allosteric modulator ( = 0), Equation 7.34 reduces to Equation 7.32. 

Used to estimate system independent potency of an allosteric modulator that affects the affinity of the agonist for the receptor but does not affect receptor signaling capability. 

FIGURE 10.19 Patterns of insurmountable blockade of receptors under conditions of (a) hemi-equilibria and (b) allosteric modulation by a modulator that only partially reduces receptor signaling, (a) Concentration-response curves to the full agonist are shifted to the right in a concentration-dependent manner. The maximal response is partially depressed and may attain a plateau level, (b) Curves are shifted to a limiting value characteristic of saturable allosteric modulation. In addition, the maximal response is depressed to a new asymptote. Note that the maximal response is not blocked to basal levels indicative of >0 (see Section 7.8.2 and Equation 7.3). 

In all cases, the molar concentration at which blockade of an agonist response is first encountered is a reasonable indication of the molecular potency of the antagonist, with the possible exception being allosteric modulators that block receptor signaling but increase the affinity of the receptor for the agonist. 

It can be seen from this example that the inhibition curve shifts to the left with increasing concentration of agonist, indicating an allosteric mechanism whereby the modulator blocks receptor signaling but increases the affinity of the receptor for the agonist. 

Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by beta-arrestins. Science 308 512-517... 

Olsson AK, Dimberg A, Kreuger J et al (2006) VEGF receptor signaling in control of vascular function. Nat Rev Mol Cell Biol 7(5) 3 59-371... 

Howlett AC (2005) Cannabinoid receptor signaling. Handb Exp Pharmacol 168 53-79... 

Fyn is a nonreceptor tyrosine kinase related to Src that is frequently found in cell junctions. Die protein is N-myristoylated and palmitoylated and thereby becomes associated with caveolae-like membrane microdomains. Fyn can interact with a variety of other signaling molecules and control a diversity of biological processes such as T cell receptor signaling, regulation of brain function, and adhesion mediated signaling. 

Loss of the cell s responsiveness to the hormone insulin caused by pathological alterations in the insulin receptor signal transduction pathway, and often leading... 

IL-1 receptor associated kinase family-A with Toll-like receptor signalling. There are four members in this group to date IRAK-1,2,4 and M. They can phosphor-ylate among themselves, as well with other proteins involved in signalling such as TRAF-6. 

Ishii I, Fukushima N, Ye X et al (2004) Lysophospholipid receptors signaling and biology. Annu Rev Biochem 73 321-354... 

Meyer zu Heringdorf D, Jakobs KH (2007) Lysophospholipid receptors signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim Biophys Acta 1768 923-940... 

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