α‐Actinin is a potent regulator of G protein‐coupled receptor kinase activity and substrate specificity in vitro

FEBS Letters

Pitcher, Julie A.¹  Lefkowitz, Robert J.¹  Li, Xiaolin¹  Freeman, Jennifer L.R.¹  Bennett, Vann¹ 

[1] Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710, USA

关键词: G protein-coupled receptor;    G protein-coupled receptor kinase;    Cytoskeleton;    Phosphatidylinositol phosphate;    Calmodulin;    Enzyme regulation;    GPCR;    G protein-coupled receptor;    GRK;    G protein-coupled receptor kinase;    ARF-GAP;    ADP-ribosylation factor-GTPase activation protein;    PIP2;    phosphatidylinositol 4;    5-bisphosphate;    PS;    phosphatidyl serine;    PKA;    protein kinase A;    β2AR;    β2-adrenergic receptor;   

DOI  :  10.1016/S0014-5793(00)01543-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

G protein-coupled receptor kinases (GRKs) phosphorylate G protein-coupled receptors, thereby terminating receptor signaling. Herein we report that α-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 α-actinin to modulate substrate specificity of the GRKs. In the presence of calmodulin and α-actinin, GRK5 phosphorylates soluble, but not membrane-incorporated substrates. In contrast, in the presence of PIP2 and α-actinin, GRK5 phosphorylates membrane-incorporated, but not soluble substrates. Thus, modulation of α-actinin-mediated inhibition of GRKs by PIP2 and calmodulin has profound effects on both GRK activity and substrate specificity.

【 授权许可】

Unknown