alpha-Actinin is a potent regulator of G protein-coupled receptor kinase activity and substrate specificity in vitro.

Published

Journal Article

G protein-coupled receptor kinases (GRKs) phosphorylate G protein-coupled receptors, thereby terminating receptor signaling. Herein we report that alpha-actinin potently inhibits all GRK family members. In addition, calcium-bound calmodulin and phosphatidylinositol 4,5-bisphosphate (PIP2), two regulators of GRK activity, coordinate with alpha-actinin to modulate substrate specificity of the GRKs. In the presence of calmodulin and alpha-actinin, GRK5 phosphorylates soluble, but not membrane-incorporated substrates. In contrast, in the presence of PIP2 and alpha-actinin, GRK5 phosphorylates membrane-incorporated, but not soluble substrates. Thus, modulation of alpha-actinin-mediated inhibition of GRKs by PIP2 and calmodulin has profound effects on both GRK activity and substrate specificity.

Full Text

Duke Authors

Cited Authors

  • Freeman, JL; Pitcher, JA; Li, X; Bennett, V; Lefkowitz, RJ

Published Date

  • May 19, 2000

Published In

Volume / Issue

  • 473 / 3

Start / End Page

  • 280 - 284

PubMed ID

  • 10818226

Pubmed Central ID

  • 10818226

International Standard Serial Number (ISSN)

  • 0014-5793

Language

  • eng

Conference Location

  • England