The G protein-coupled receptor kinase 2 is a microtubule-associated protein kinase that phosphorylates tubulin.

Published

Journal Article

The G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase that phosphorylates and desensitizes agonist-occupied G protein-coupled receptors (GPCRs). Here we demonstrate that GRK2 is a microtubule-associated protein and identify tubulin as a novel GRK2 substrate. GRK2 is associated with microtubules purified from bovine brain, forms a complex with tubulin in cell extracts, and colocalizes with tubulin in living cells. Furthermore, an endogenous tubulin kinase activity that copurifies with microtubules has properties similar to GRK2 and is inhibited by anti-GRK2 monoclonal antibodies. Indeed, GRK2 phosphorylates tubulin in vitro with kinetic parameters very similar to those for phosphorylation of the agonist-occupied beta2-adrenergic receptor, suggesting a functionally relevant role for this phosphorylation event. In a cellular environment, agonist occupancy of GPCRs, which leads to recruitment of GRK2 to the plasma membrane and its subsequent activation, promotes GRK2-tubulin complex formation and tubulin phosphorylation. These findings suggest a novel role for GRK2 as a GPCR signal transducer mediating the effects of GPCR activation on the cytoskeleton.

Full Text

Duke Authors

Cited Authors

  • Pitcher, JA; Hall, RA; Daaka, Y; Zhang, J; Ferguson, SS; Hester, S; Miller, S; Caron, MG; Lefkowitz, RJ; Barak, LS

Published Date

  • May 1998

Published In

Volume / Issue

  • 273 / 20

Start / End Page

  • 12316 - 12324

PubMed ID

  • 9575184

Pubmed Central ID

  • 9575184

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.273.20.12316

Language

  • eng