Genetic Analysis of the β-Adrenergic Receptor
Perhaps the largest class of hormone and neurotransmitter receptors is those whose signal transduction pathways involve the activation of guanine nucleotide binding regulatory proteins (G-proteins). Hormones which activate such receptors are prevalent in both the central nervous system and the periphery, and include glycoproteins (lutropin, thyrotropin), peptides (neurokinins, angiotensin), and small molecules (retinal, biogenic amines). The signal tranduction pathway common to these systems is initiated by the binding of the ligand to the cell-surface receptor. The agonist-bound receptor interacts with a G-protein, forming a high-affinity ternary hormone-receptor-G-protein complex, and catalyzing the exchange of GDP for GTP in the nucleotide binding site of the G-protein (Gilman, 1987). This nucleotide exchange reaction activates the G-protein and destabilizes the ternary complex. The activated G-protein then interacts with effector systems, leading to the modulation of intracellular second messenger levels. Effector systems which are activated by G-protein coupled pathways include adenylyl cyclase, guanylyl cyclase, phospholipases A and C, phosphodiesterases, Ca++ and K+ channels, and ion co-transport systems.
KeywordsAdenylyl Cyclase Transmembrane Helix Intracellular Loop Wasp Venom Deletion Mutagenesis
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