Linked Life Data

12376539

Source:http://linkedlifedata.com/resource/pubmed/id/12376539

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2002-12-23
pubmed:abstractText
The present studies demonstrate that no single stretch of sequence in the third intracellular (3i) loop of the alpha(2A) adrenergic receptor (alpha(2A)-AR) can fully account for its previously described interactions with spinophilin (Richman, J. G., Brady, A. E., Wang, Q., Hensel, J. L., Colbran, R. J., and Limbird, L. E. (2001) J. Biol. Chem. 276, 15003-15008), 14-3-3zeta (Prezeau, L., Richman, J. G., Edwards, S. W., and Limbird, L. E. (1999) J. Biol. Chem. 274, 13462-13469), and arrestin 3 (Wu, G., Krupnick, J. G., Benovic, J. L., and Lanier, S. M. (1997) J. Biol. Chem. 272, 17836-17842), suggesting that a three-dimensional surface, rather than a linear sequence, provides the basis for these interactions as proposed for 3i loop tethering of the alpha(2A)-AR to the basolateral surface of Madin-Darby canine kidney cells (Edwards, S. W., and Limbird, L. E. (1999) J. Biol. Chem. 274, 16331-16336). Sequences at the extreme N-terminal and C-terminal ends of the 3i loop are critical for interaction with spinophilin but not for interaction with 14-3-3zeta or arrestin 3, for which the C-terminal half of the loop is more important. Competition binding for (35)S-labeled alpha(2A)-AR 3i loop binding to glutathione S-transferase (GST)-spinophilin amino acids 151-444 revealed a relative affinity of spinophilin congruent with arrestin > 14-3-3zeta for the unphosphorylated alpha(2A)-AR 3i loop. Agonist occupancy of the alpha(2A)-AR increases receptor association with spinophilin, and arrestin 3 appears to compete for this enrichment. However, when the G protein-coupled receptor kinase 2 substrate sequence was deleted from the 3i loop, arrestin 3 could not compete for the agonist-enriched binding of spinophilin to the mutant alpha(2A)-AR. These data are consistent with a model where sequential or competitive interactions among spinophilin, arrestin, and/or 14-3-3zeta play a role in alpha(2A)-AR functions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
50589-96
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12376539-Amino Acid Substitution, pubmed-meshheading:12376539-Animals, pubmed-meshheading:12376539-Arrestins, pubmed-meshheading:12376539-Binding, Competitive, pubmed-meshheading:12376539-Binding Sites, pubmed-meshheading:12376539-Cell Line, pubmed-meshheading:12376539-Dogs, pubmed-meshheading:12376539-Kidney, pubmed-meshheading:12376539-Kinetics, pubmed-meshheading:12376539-Microfilament Proteins, pubmed-meshheading:12376539-Models, Molecular, pubmed-meshheading:12376539-Nerve Tissue Proteins, pubmed-meshheading:12376539-Peptide Fragments, pubmed-meshheading:12376539-Protein Structure, Secondary, pubmed-meshheading:12376539-Receptors, Adrenergic, alpha-2, pubmed-meshheading:12376539-Recombinant Proteins, pubmed-meshheading:12376539-Sequence Alignment, pubmed-meshheading:12376539-Sequence Deletion, pubmed-meshheading:12376539-Sequence Homology, Amino Acid
pubmed:year
2002
pubmed:articleTitle
Regulated interactions of the alpha 2A adrenergic receptor with spinophilin, 14-3-3zeta, and arrestin 3.
pubmed:affiliation
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.