Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1995-6-12
pubmed:abstractText
The NH2 terminus of insulin receptor substrate-1 (IRS-1) contains a pleckstrin homology (PH) domain. We deleted the PH domain in IRS-1 (IRS-1 delta PH) and expressed the mutant in Chinese hamster ovary and 32D cells. During insulin stimulation, IRS-1 delta PH is poorly tyrosine-phosphorylated in CHO cells, but undergoes serine/threonine phosphorylation. Similarly, IRS-1 delta PH fails to undergo insulin-stimulated tyrosine phosphorylation in 32D cells, which uncouples the activation of phosphatidylinositol 3'-kinase and p70s6k from the endogenous insulin receptors. Overexpression of the insulin receptor in 32DIR cells, however, restores tyrosine phosphorylation of IRS-1 delta PH and rescues insulin responses including mitogenesis. Thus, while the PH domain is not required for the engagement of downstream signals, it is one of the elements in the NH2 terminus of IRS-1 that is needed for a sensitive coupling to insulin receptors, especially at ordinary receptor levels found in most cells and tissues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11715-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:7744813-Animals, pubmed-meshheading:7744813-Base Sequence, pubmed-meshheading:7744813-Blood Proteins, pubmed-meshheading:7744813-CHO Cells, pubmed-meshheading:7744813-Cell Line, pubmed-meshheading:7744813-Cricetinae, pubmed-meshheading:7744813-Humans, pubmed-meshheading:7744813-Insulin, pubmed-meshheading:7744813-Insulin Receptor Substrate Proteins, pubmed-meshheading:7744813-Mice, pubmed-meshheading:7744813-Molecular Sequence Data, pubmed-meshheading:7744813-Phosphoproteins, pubmed-meshheading:7744813-Phosphorylation, pubmed-meshheading:7744813-Protein Processing, Post-Translational, pubmed-meshheading:7744813-Protein Structure, Tertiary, pubmed-meshheading:7744813-Rats, pubmed-meshheading:7744813-Receptor, Insulin, pubmed-meshheading:7744813-Sequence Deletion, pubmed-meshheading:7744813-Sequence Homology, Amino Acid, pubmed-meshheading:7744813-Signal Transduction, pubmed-meshheading:7744813-Species Specificity, pubmed-meshheading:7744813-Up-Regulation
pubmed:year
1995
pubmed:articleTitle
The pleckstrin homology domain in insulin receptor substrate-1 sensitizes insulin signaling.
pubmed:affiliation
Research Division, Joslin Diabetes Center, Bethesda, Maryland, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't