Structural highlights
Function
ARBK1_BOVIN Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The phosphorylation of heptahelical receptors by heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor kinases (GRKs) is a universal regulatory mechanism that leads to desensitization of G protein signaling and to the activation of alternative signaling pathways.We determined the crystallographic structure of bovine GRK2 in complex with G protein beta1gamma2 subunits.Our results show how the three domains of GRK2-the RGS (regulator of G protein signaling) homology, protein kinase, and pleckstrin homology domains-integrate their respective activities and recruit the enzyme to the cell membrane in an orientation that not only facilitates receptor phosphorylation, but also allows for the simultaneous inhibition of signaling by Galpha and Gbetagamma subunits.
Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.,Lodowski DT, Pitcher JA, Capel WD, Lefkowitz RJ, Tesmer JJ Science. 2003 May 23;300(5623):1256-62. PMID:12764189[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lodowski DT, Pitcher JA, Capel WD, Lefkowitz RJ, Tesmer JJ. Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma. Science. 2003 May 23;300(5623):1256-62. PMID:12764189 doi:http://dx.doi.org/10.1126/science.1082348
