| Heterotrimeric G protein-mediated signal transduction is a dynamically regulated process with the intensity of signal decreasing over time despite the continued presence of the agonist. This phenomenon, referred to as agonist-mediated desensitization, involves phosphorylation of the receptor by two classes of enzymes. The first is the second messenger regulated kinases such as cAMP dependent protein kinase A and protein kinase C. The second is the G protein-coupled receptor kinases (GRKs). Six members of the GRK family have been identified to date. These include rhodopsin kinase (GRK 1), two forms of beta-adrenergic receptor kinase (GRK 2 or beta-ARK 1 and GRK 3 or beta-ARK 2), IT-11 (GRK 4), GRK 5 and GRK 6. Phosphorylation of receptors by GRKs appears to be strictly dependent on the receptor being in its agonist-activated state. |
