Isolation of a novel visual-system-specific arrestin: an in vivo substrate for light-dependent phosphorylation.
Absorption of a photon of light by rhodopsin triggers mechanisms responsible for excitation as well as regulation of the phototransduction cascade. Arrestins are a family of proteins that appear to be responsible for terminating the active state of G-protein-coupled receptors. One of the major substrates of light-dependent phosphorylation in the visual cascade of Drosophila was purified and partially sequenced. The complete primary structure of the protein was determined by isolating the corresponding gene, which revealed it to be a new isoform of arrestin, Arr2. Arr2 is 401 residues in length, and shares 47% sequence identity with the Drosophila Arr1 protein and 42% with human arrestin. We show that the two Drosophila arrestin genes are differentially regulated, and that Arr2 is a specific substrate for a calcium-dependent protein kinase. This is the first demonstration of in vivo regulation of arrestins in a transduction cascade, and provides a new level of modulation in the function of G-protein-coupled receptors.
LeVine
H
H
Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093.
Smith
D P
DP
Whitney
M
M
Malicki
D M
DM
Dolph
P J
PJ
Smith
G F
GF
Burkhart
W
W
Zuker
C S
CS
D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins; D001483:Base Sequence; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000737:chemistry* / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000302:isolation & purification*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D008027:Light; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000302:isolation & purification*; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012243:Rhodopsin / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction; D017871:Calcium-Calmodulin-Dependent Protein Kinases
D019390:Arrestins; D029721:Drosophila Proteins; D005136:Eye Proteins; D019204:GTP-Binding Proteins; D010750:Phosphoproteins; D011494:Protein Kinases; D012243:Rhodopsin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C504665:Arr1 protein, Drosophila