Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases.

Journal Article

Rhodopsin kinase and beta-adrenergic receptor kinase (beta ARK) are related members of a serine/threonine kinase family that specifically initiate deactivation of G-protein-coupled receptors. After stimulus-mediated receptor activation, these cytoplasmic kinases translocate to the plasma membrane. Here we show that the molecular basis for this event involves a class of unsaturated lipids called isoprenoids. Covalent modification in vivo of rhodopsin kinase by a 15-C (farnesyl) isoprenoid enables the kinase to anchor to photon-activated rhodopsin. Mutations that alter or eliminate the isoprenoid, fully disable light-specific Rhodopsin kinase translocation. Other receptor kinases (such as beta ARK), which lack an intrinsic lipid, are activated on exposure to brain beta gamma subunits of the signal-transducing G proteins, the gamma subunit of which bears a 20-C (geranylgeranyl) isoprenoid. Using chimaeric beta ARKs that undergo isoprenylation in vitro, we demonstrate that membrane association and activation of these kinases can occur in the absence of beta gamma. These results indicate that rhodopsin kinase (by means of an integral isoprenoid) and beta ARK (through its association with beta gamma) both rely on the function of isoprenyl moieties for their translocation and activity, illustrating distinct, though related, modes of biological regulation of receptor function.

Full Text

Duke Authors

Cited Authors

  • Inglese, J; Koch, WJ; Caron, MG; Lefkowitz, RJ

Published Date

  • September 10, 1992

Published In

Volume / Issue

  • 359 / 6391

Start / End Page

  • 147 - 150

PubMed ID

  • 1522899

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/359147a0

Language

  • eng

Conference Location

  • England