Receptor signaling antagonism

Kim, J., Ahn, S., Ren, X. R., et al. 2005b. Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling. Proc Natl Acad SciUSA 102 1442-1447. 

Luttrell, L.M., Ostrowski, J., Cotecchia, S., Kendall, H., and Lefkowitz, R.J. (1993). Antagonism of catecholamine receptor signalling by expression of cytoplasmic domains of the receptors. Science 259, 1453 1457. 

Castrillo A, Joseph SB, Vaidya SA, et al. Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism. Mol Cell 2003 12 805-816. 

If the antagonism is insurmountable, then there are a number of molecular mechanisms possible. The next question to ask is if the maximal response to the agonist can be completely depressed to basal levels. If this is not the case, then there could be partial allosteric alteration of the signaling properties of the receptor. Alternatively, this could be due to a hemi-equilibrium condition that produces a partial shortfall to true competitive equilibrium, leading to incomplete depression of the maximal response but also antagonist concentration-related dextral displacement of the concentration response curve to the agonist (see Figure 10.19a). The model (see Section 10.6.5) used to fit these data is discussed in Section 6.5 and shown in... 

---