alpha-Actinin is a potent regulator of G protein-coupled receptor kinase activity and substrate specificity in vitro.
Journal Article (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.
- Freeman, JL; Pitcher, JA; Li, X; Bennett, V; Lefkowitz, RJ
- May 19, 2000
Volume / Issue
- 473 / 3
Start / End Page
- 280 - 284
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)