alpha-Actinin is a potent regulator of G protein-coupled receptor kinase activity and substrate specificity in vitro.
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.
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- beta-Adrenergic Receptor Kinases
- Substrate Specificity
- Rhodopsin
- Protein Serine-Threonine Kinases
- Phosphorylation
- Phosphatidylinositol 4,5-Diphosphate
- G-Protein-Coupled Receptor Kinase 5
- Cyclic AMP-Dependent Protein Kinases
- Chickens
- Caseins
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- beta-Adrenergic Receptor Kinases
- Substrate Specificity
- Rhodopsin
- Protein Serine-Threonine Kinases
- Phosphorylation
- Phosphatidylinositol 4,5-Diphosphate
- G-Protein-Coupled Receptor Kinase 5
- Cyclic AMP-Dependent Protein Kinases
- Chickens
- Caseins