Light-dependent phosphorylation of rhodopsin by |[beta]|-adrenergic receptor kinase

The structural components involved in transduction of extracellular signals as diverse as a photon of light impinging on the retina or a hormone molecule impinging on a cell have been highly conserved. These components include a recognition unit or receptor (for example, the β-adrenergic receptor (βAR) for catecholamines or the ‘light receptor’ rhodopsin), a guanine nucleotide regulatory or transducing protein, and an effector enzyme (for example, adenylate cyclase or cyclic GMP phosphodiesterase)1,2. Molecular cloning has revealed that the βAR shares significant sequence and three-dimensional homology with rhodopsin3. The function of the βAR is diminished by exposure to stimulatory agonists, leading to desensitization4. Similarly, ‘light adaptation’ involves decreased coupling of photoactivated rhodopsin to cGMP phosphodiesterase activation5–7. Both forms of desensitization involve receptor phosphorylation. The latter is mediated by a unique protein kinase, rhodopsin kinase, which phosphorylates only the light-bleached form of rhodopsin8–10. An analogous enzyme (termed βAR kinase or βARK) phosphorylates only the agonist-occupied βAR11. We report here that βARK is also capable of phosphorylating rhodopsin in a totally light-dependent fashion. Moreover, rhodopsin kinase can phosphorylate the agonist-occupied βAR. Thus the mechanisms which regulate the function of these disparate signalling systems also appear to be similar.