Linked Life Data

10332026

Source:http://linkedlifedata.com/resource/pubmed/id/10332026

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-7-8
pubmed:databankReference
pubmed:abstractText
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neuro degrees enerative disorder associated with CAG/glutamine repeat expansion. While the DRPLA gene is ubiquitously expressed, neuron death occurs in specific anatomical areas of the brain. This predicts that the DRPLA protein interacts with other proteins and that these interactions may play a role in pathogenesis. Here, we describe a protein that binds to the DRPLA product. One of the clones isolated with a yeast two-hybrid system was identified as a human homolog of the insulin receptor tyrosine kinase substrate protein of 53 kDa (IRSp53). The gene produced two mRNA forms by differential splicing and encoded 552 and 521 amino acids, respectively. The longer form was mainly expressed in the brain and the shorter one in other tissues. The products were phosphorylated upon stimulation of cultured cells with insulin or insulin-like growth factor 1. Binding of the DRPLA protein to IRSp53 was ascertained by co-immunoprecipitation with antibodies and also by co-localization in perinuclear oval dots in cells expressing engineered constructs. A proline-rich region near the polyglutamine tract of the DRPLA protein and the SH3 domain of IRSp53 were involved in the binding. An extended polyglutamine tract significantly reduced binding ability in yeast cells, but not in in vitro binding assays. The identification of IRSp53 and other proteins detected by the yeast hybrid system predicts that DRPLA functions in a signal transduction pathway coupled with insulin/IGF-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
947-57
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10332026-Amino Acid Sequence, pubmed-meshheading:10332026-Animals, pubmed-meshheading:10332026-Binding Sites, pubmed-meshheading:10332026-DNA, Complementary, pubmed-meshheading:10332026-HeLa Cells, pubmed-meshheading:10332026-Humans, pubmed-meshheading:10332026-Molecular Sequence Data, pubmed-meshheading:10332026-Nerve Tissue Proteins, pubmed-meshheading:10332026-PC12 Cells, pubmed-meshheading:10332026-Peptides, pubmed-meshheading:10332026-Phosphorylation, pubmed-meshheading:10332026-Plasmids, pubmed-meshheading:10332026-Precipitin Tests, pubmed-meshheading:10332026-Proline, pubmed-meshheading:10332026-Protein Binding, pubmed-meshheading:10332026-Proteins, pubmed-meshheading:10332026-Rats, pubmed-meshheading:10332026-Receptor, Insulin, pubmed-meshheading:10332026-Recombinant Fusion Proteins, pubmed-meshheading:10332026-Saccharomyces cerevisiae, pubmed-meshheading:10332026-Sequence Analysis, DNA, pubmed-meshheading:10332026-Sequence Homology, Amino Acid, pubmed-meshheading:10332026-Substrate Specificity, pubmed-meshheading:10332026-src Homology Domains
pubmed:year
1999
pubmed:articleTitle
Dentatorubral-pallidoluysian atrophy protein interacts through a proline-rich region near polyglutamine with the SH3 domain of an insulin receptor tyrosine kinase substrate.
pubmed:affiliation
Department of Genetics, National Children's Memorial Medical Research Center, Taishido, Setagaya, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't