Light-dependent phosphorylation of rhodopsin by β-adrenergic receptor kinase

Abstract

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 activation^5–7. 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 rhodopsin^8–10. 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.