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Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family
Ist Teil von
The Journal of biological chemistry, 1992-09, Vol.267 (25), p.17882-17890
Ort / Verlag
Bethesda, MD: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1992
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Homologous or agonist-specific desensitization of beta 2-adrenergic receptors (beta 2AR) is mediated by the beta-adrenergic
receptor kinase (beta ARK) which specifically phosphorylates the agonist-occupied form of the receptor. However, the capacity
of beta ARK-phosphorylated beta 2AR to stimulate Gs in a reconstituted system is only minimally impaired. Recently, a protein
termed beta-arrestin, was cloned from a bovine brain cDNA library and found to quench phosphorylated beta 2AR-coupling to
Gs. Utilizing a low stringency hybridization technique to screen a rat brain cDNA library, we have now isolated cDNA clones
representing two distinct beta-arrestin-like genes. One of the cDNAs is the rat homolog of bovine beta-arrestin (beta-arrestin1).
In addition, we have isolated a cDNA clone encoding a novel, beta-arrestin-related protein which we have termed beta-arrestin2.
Overall, beta-arrestin2 exhibits 78% amino acid identity with beta-arrestin1. The primary structure of these proteins delineates
a family of proteins that regulates receptor coupling to G proteins. The capacity of purified beta-arrestin1, beta-arrestin2,
and arrestin to inhibit the coupling of phosphorylated receptors to their respective G proteins were assessed in a reconstituted
beta 2AR-Gs system and in a reconstituted rhodopsin-GT system. beta-Arrestin2 was equipotent to beta-arrestin1 and specifically
inhibited beta 2AR function. Conversely, arrestin inhibited rhodopsin coupling to GT, whereas beta-arrestin1 and beta-arrestin2
were at least 20-fold less potent in this system. beta-Arrestin1 and beta-arrestin2 are predominantly localized in neuronal
tissues and in the spleen. However, low mRNA levels can be detected in most peripheral tissues. In the central nervous system,
beta-arrestin2 appears to be even more abundant than beta-arrestin1. Immunohistochemical analysis of the tissue distribution
of beta-arrestin1 and beta-arrestin2 in rat brain shows extensive, but heterogenous, neuronal labeling of the two proteins.
They are found in several neuronal pathways suggesting that they have relatively broad receptor specificity regulating many
G protein-coupled receptors. Furthermore, immunoelectron microscopy shows that the beta-arrestins are appropriately situated
at postsynaptic sites to act in concert with beta ARK to regulate G protein-coupled neurotransmitter receptors.