Publication Date:
2003-05-24
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lodowski, David T -- Pitcher, Julie A -- Capel, W Darrell -- Lefkowitz, Robert J -- Tesmer, John J G -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 May 23;300(5623):1256-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12764189" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
Amino Acid Sequence
;
Animals
;
Cattle
;
Cell Membrane/metabolism
;
Crystallography, X-Ray
;
Cyclic AMP-Dependent Protein Kinases/*chemistry/*metabolism
;
*GTP-Binding Protein beta Subunits
;
*GTP-Binding Protein gamma Subunits
;
Heterotrimeric GTP-Binding Proteins/*chemistry/*metabolism
;
Hydrophobic and Hydrophilic Interactions
;
Models, Molecular
;
Molecular Sequence Data
;
Phosphorylation
;
Protein Binding
;
Protein Conformation
;
Protein Structure, Quaternary
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Signal Transduction
;
beta-Adrenergic Receptor Kinases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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