Linked Life Data

17456469

Source:http://linkedlifedata.com/resource/pubmed/id/17456469

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2007-6-25
pubmed:abstractText
The highly homologous beta-arrestin1 and -2 adaptor proteins play important roles in the function of G protein-coupled receptors. Either beta-arrestin variant can function as a molecular chaperone for clathrin-mediated receptor internalization. This role depends primarily upon two distinct, contiguous C-terminal beta-arrestin motifs recognizing clathrin and the beta-adaptin subunit of AP2. However, a molecular basis is lacking to explain the different endocytic efficacies of the two beta-arrestin isoforms and the observation that beta-arrestin N-terminal substitution mutants can act as dominant negative inhibitors of receptor endocytosis. Despite the near identity of the beta-arrestins throughout their N termini, sequence variability is present at a small number of residues and includes tyrosine to phenylalanine substitutions. Here we show that corresponding N-terminal (Y/F)VTL sequences in beta-arrestin1 and -2 differentially regulate mu-adaptin binding. Our results indicate that the beta-arrestin1 Tyr-54 lessens the interaction with mu-adaptin and moreover is a Src phosphorylation site. A gain of endocytic function is obtained with the beta-arrestin1 Y54F substitution, which improves both the beta-arrestin1 interaction with mu-adaptin and the ability to enhance beta2-adrenergic receptor internalization. These data indicate that beta-arrestin2 utilizes mu-adaptin as an endocytic partner, and that the inability of beta-arrestin1 to sustain a similar degree of interaction with mu-adaptin may result from coordination of Tyr-54 by neighboring residues or its modification by Src kinase. Additionally, these naturally occurring variations in beta-arrestins may also differentially regulate the composition of the signaling complexes organized on the receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18937-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17456469-Adaptor Protein Complex mu Subunits, pubmed-meshheading:17456469-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:17456469-Amino Acid Sequence, pubmed-meshheading:17456469-Amino Acid Substitution, pubmed-meshheading:17456469-Animals, pubmed-meshheading:17456469-Arrestins, pubmed-meshheading:17456469-Cell Line, pubmed-meshheading:17456469-Clathrin-Coated Vesicles, pubmed-meshheading:17456469-Humans, pubmed-meshheading:17456469-Kidney, pubmed-meshheading:17456469-Molecular Sequence Data, pubmed-meshheading:17456469-Mutagenesis, Site-Directed, pubmed-meshheading:17456469-Phenylalanine, pubmed-meshheading:17456469-Phosphorylation, pubmed-meshheading:17456469-Protein Structure, Tertiary, pubmed-meshheading:17456469-Rats, pubmed-meshheading:17456469-Transport Vesicles, pubmed-meshheading:17456469-Tyrosine, pubmed-meshheading:17456469-src-Family Kinases
pubmed:year
2007
pubmed:articleTitle
N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins.
pubmed:affiliation
Department of Cell Biology, Duke University, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural