Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes.

Journal Article (Journal Article)

The Ras-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of beta2 adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by beta-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. beta-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of beta2 adrenergic receptor-mediated activation of the MAP kinases Erk1 and Erk2. These data suggest that beta-arrestin binding, which terminates receptor-G protein coupling, also initiates a second wave of signal transduction in which the "desensitized" receptor functions as a critical structural component of a mitogenic signaling complex.

Full Text

Duke Authors

Cited Authors

  • Luttrell, LM; Ferguson, SS; Daaka, Y; Miller, WE; Maudsley, S; Della Rocca, GJ; Lin, F; Kawakatsu, H; Owada, K; Luttrell, DK; Caron, MG; Lefkowitz, RJ

Published Date

  • January 29, 1999

Published In

Volume / Issue

  • 283 / 5402

Start / End Page

  • 655 - 661

PubMed ID

  • 9924018

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.283.5402.655


  • eng

Conference Location

  • United States