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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Robinson, P. R. Ohguro, H. Buczylko, J. Palczewski, K. |
| Description | Author Affiliation: Robinson PR ( Department of Biological Sciences, University of Maryland Baltimore County, Baltimore 21228.); |
| Abstract | More than 70 mutations in the gene encoding the visual pigment rhodopsin have been identified in patients with autosomal dominant retinitis pigmentosa. Most of these mutations are thought to interfere with proper folding of the membrane protein. However, families with a severe phenotype of retinitis pigmentosa have been identified and shown to carry a mutation at the site of chromophore attachment, Lys-296. This mutation disrupts the inactive conformation of opsin and results in a constitutively active protein that can activate the rod-specific GTP-binding protein, transducin, in the absence of light and in the absence of the chromophore 11-cis-retinal. It has been suggested that this mutant opsin molecule may cause rod degeneration by depletion of the components used to inactivate rhodopsin, such as rhodopsin kinase. In this work we test this idea by determining whether two constitutively active opsin mutants are phosphorylated by rhodopsin kinase. We found that opsin mutants where Lys-296 is replaced either by Glu (K296E) or by Gly (K296G) are not substrates of rhodopsin kinase in the absence of chromophore. However, when K296G is regenerated with a Schiff base complex of 11-cis-retinal and n-propylamine and exposed to illumination, phosphorylation of opsin occurs. These experiments suggest that in the rod photoreceptors of patients with retinitis pigmentosa carrying a mutation at Lys-296, there is persistent activation of the GTP-binding protein-mediated cascade. This may result in a situation that mimics long-term exposure to continuous illumination and results in the degeneration of photoreceptors. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 91 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1994-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Eye Proteins Protein Kinases Genetics Rod Opsins Metabolism Transducin Amino Acid Sequence Animals Cell Line Cell Membrane Cercopithecus Aethiops G-Protein-Coupled Receptor Kinase 1 Molecular Sequence Data Mutagenesis, Site-Directed Mutation Peptides Chemistry Phosphoproteins Phosphorylation Protein Conformation Recombinant Proteins Structure-Activity Relationship Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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