Polypeptide variants of beta-arrestin and arrestin3.
Retinal arrestin (S-antigen) inactivates the phototransduction cascade by binding to light-activated phosphorylated rhodopsin and thereby "arresting" coupling to the G protein transducin. beta-Arrestin (beta arr), a ubiquitous arrestin homolog, acts analogously to desensitize the beta 2-adrenergic receptor by disrupting Gs receptor interaction. In an attempt to identify additional "arrestins" which might regulate the multitude of G protein-coupled receptors, we have isolated two bovine brain cDNAs which encode polypeptide variants of an arrestin homolog which we have designated arrestin3 (arr3). The open reading frames of these two cDNAs are identical except that the long form, arr3L, contains an 11-amino-acid insert between residues 361 and 362. Arr3 is more closely related to bovine beta arr (78% identity) than to bovine visual arrestin (56% identity). Polymerase chain reaction amplification of RNA and immunoblotting of lysates with an arr3-specific antibody suggest that the short form, arr3S, is the major form of arr3 in all bovine tissues and that it is most abundant in the spleen. Furthermore, polymerase chain reaction amplification of beta arr mRNA indicates that in several tissues (lung, liver, spleen, and pituitary), the major form of beta arr lacks 8 amino acids which are present in brain beta arr. Immunoblotting with an antibody which recognizes beta arr and arr3 with equal sensitivity demonstrates that beta arr (either the long or the short polypeptide) is the major arrestin in all (non-photoreceptor bearing) tissues examined. These observations suggest that in some tissues, as many as four arrestin homolog variants may play a role in the regulation of G protein-coupled receptors.
Sterne-Marr
R
R
Department of Pharmacology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Gurevich
V V
VV
Goldsmith
P
P
Bodine
R C
RC
Sanders
C
C
Donoso
L A
LA
Benovic
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000235:genetics*; D019393:Arrestin; D019390:Arrestins; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000071557:beta-Arrestins
D000941:Antigens; D019393:Arrestin; D019390:Arrestins; D005136:Eye Proteins; D010455:Peptides; D012333:RNA, Messenger; C082333:arrestin3; D000071557:beta-Arrestins; D004247:DNA