GRKs bind ADRB2:Catecholamine

Stable Identifier
R-HSA-8982645
Type
Reaction
Species
Homo sapiens
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Summation

G protein-coupled receptor kinase 2 (ADRBK1, GRK2, beta-ARK), ADRBK2 (GRK3, beta-ARK2), GRK5 and GRK6 can phosphorylate activated beta-adrenergic receptors (Benovic et al. 1986a, Richardson et al. 1993, Menard et al. 1996, Violin et al. 2006). GRK2, GRK5 and GRK6 can bind to beta-2 adrenergic receptor (ADRB2) and subsequently phosphorylate them in the carboxy-terminal tail region (Premont et al. 1994, 1995, Violin et al. 2006). GRK2 and GRK6 are thought to be the predominant GRKs that mediate ADRB2 desensitization (Violin et al. 2006), phosphorylating distinct serine residues (Nobles et al. 2011).

GRK phosphorylation follwed by arrestin binding and internalization is the classical model for GPCR desensitization. Many GPCRs have been demonstrated to require phosphorylation before they can bind arrestin, but other receptors do not appear to require phosphorylation in order to bind arrestin (see refs included in Gurevich & Gurevich 2006). In these receptors, spatially close acidic amino acids are thought to provide sites that can bind the arrestin phosphate sensing region. In GPCRs that require phosphorylation, the region most commonly involved in arrestin binding is the C-terminus, but many GPCRs have phosphorylation sites in the 3rd cytoplasmic loop, while in some cases phosphorylation sites are found in the first (i1) or second (i2) cytoplasmic loops (Gurevich & Gurevich 2006).

Literature References
PubMed ID Title Journal Year
2871555 Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor

Benovic, JL, Strasser, RH, Caron, MG, Lefkowitz, RJ

Proc. Natl. Acad. Sci. U.S.A. 1986
8514797 Phosphorylation and desensitization of human m2 muscarinic cholinergic receptors by two isoforms of the beta-adrenergic receptor kinase

Richardson, RM, Kim, C, Benovic, JL, Hosey, MM

J. Biol. Chem. 1993
16687412 G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by fluorescence resonance energy transfer

Violin, JD, Ren, XR, Lefkowitz, RJ

J. Biol. Chem. 2006
8672451 Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration

Ménard, L, Ferguson, SS, Barak, LS, Bertrand, L, Premont, RT, Colapietro, AM, Lefkowitz, RJ, Caron, MG

Biochemistry 1996
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