A RNA molecule that specifically inhibits G-protein coupled receptor kinase 2 in vitro

Mayer, G. and Wulffen, Bernhard and Huber, Christian and Brockmann, Joerg and Flicke, Birgit and Neumann, Lars and Hafenbradl, Doris and Klebl, Bert M. (2008) A RNA molecule that specifically inhibits G-protein coupled receptor kinase 2 in vitro. RNA - A Publication of the RNA Society, 14 (3). pp. 524-534. ISSN 1355-8382 (http://dx.doi.org/10.1261/rna.821908)

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Abstract

G-protein-coupled receptors are desensitized by a two-step process. In a first step, G-protein-coupled receptor kinases (GRKs) phosphorylate agonist-activated receptors that subsequently bind to a second class of proteins, the arrestins. GRKs can be classified into three subfamilies, which have been implicated in various diseases. The physiological role(s) of GRKs have been difficult to study as selective inhibitors are not available. We have used SELEX (systematic evolution of ligands by exponential enrichment) to develop RNA aptamers that potently and selectively inhibit GRK2. This process has yielded an aptamer, C13, which bound to GRK2 with a high affinity and inhibited GRK2-catalyzed rhodopsin phosphorylation with an IC50 of 4.1 nM. Phosphorylation of rhodopsin catalyzed by GRK5 was also inhibited, albeit with 20-fold lower potency (IC50 of 79 nM). Furthermore, C13 reveals significant specificity, since almost no inhibitory activity was detectable testing it against a panel of 14 other kinases. The aptamer is two orders of magnitude more potent than the best GRK2 inhibitors described previously and shows high selectivity for the GRK family of protein kinases.

  • Item type:Article
    ID code:26100
    Dates:
    Date
    Event
    March 2008
    Published
    Notes:Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.
    Subjects:Science > Chemistry
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Strathprints Administrator
    Date deposited:19 Aug 2010 14:19
    Last modified:08 Apr 2024 18:15
    URI:https://strathprints.strath.ac.uk/id/eprint/26100
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