Linked Life Data

7852347

Source:http://linkedlifedata.com/resource/pubmed/id/7852347

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-3-16
pubmed:abstractText
The amino acid sequence of the tyrosine kinase domain of the insulin-like growth factor-I (IGF-I) receptor is 84% identical to the sequence of the analogous region of the insulin receptor. A naturally occurring mutation of the tryptophan residue at position 1200 of the insulin receptor to serine results in impaired beta subunit autophosphorylation of wheat germ agglutinin-purified receptors, severely impaired thymidine incorporation and moderately reduced glycogen synthesis; however, glucose uptake was unaffected. To study the importance of this residue in IGF-I receptor function, we mutated the analogous tryptophan residue at position 1173 of the IGF-I receptor to serine and overexpressed the mutant receptor in NIH-3T3 cells. In cell lines overexpressing this mutant IGF-I receptor, beta subunit autophosphorylation was severely reduced. Additionally, the overexpressed mutant receptors exhibited a dominant-negative effect on IGF-I-stimulated autophosphorylation of endogenous mouse IGF-I receptors. Phosphorylation of insulin receptor substrate (IRS)-1 in intact cells by the mutant IGF-I receptors was similar to the level of IRS-1 phosphorylation seen in the parental NIH-3T3 cells, but there was no obvious dominant-negative effect on IRS-1 phosphorylation. Wheat germ agglutinin-purified mutant receptors were as active in phosphorylating poly-(Glu,Tyr) 4:1 as wild-type IGF-I receptors, suggesting that, in intact cells, additional factors are necessary in order for the IGF-I receptor to phosphorylate IRS-1. Thymidine incorporation was severely reduced in one clone overexpressing the mutant IGF-I receptor and abolished in a second clone. Glucose uptake in both clones was reduced to about half of that seen in a cell line over-expressing wild-type IGF-I receptors. Thus, we propose that the tryptophan residue at position 1173 of the IGF-I receptor is important in the regulation of autophosphorylation in vivo. This study again confirms that high levels of autophosphorylation are not required for mediation of all of the biologic activities of the IGF-I receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2764-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7852347-3T3 Cells, pubmed-meshheading:7852347-Amino Acid Sequence, pubmed-meshheading:7852347-Animals, pubmed-meshheading:7852347-Base Sequence, pubmed-meshheading:7852347-Binding Sites, pubmed-meshheading:7852347-Conserved Sequence, pubmed-meshheading:7852347-DNA Primers, pubmed-meshheading:7852347-Deoxyglucose, pubmed-meshheading:7852347-Mice, pubmed-meshheading:7852347-Molecular Sequence Data, pubmed-meshheading:7852347-Mutation, pubmed-meshheading:7852347-Phosphorylation, pubmed-meshheading:7852347-Protein-Tyrosine Kinases, pubmed-meshheading:7852347-Receptors, Somatomedin, pubmed-meshheading:7852347-Signal Transduction, pubmed-meshheading:7852347-Thymidine, pubmed-meshheading:7852347-Tryptophan, pubmed-meshheading:7852347-Tyrosine, pubmed-meshheading:7852347-Wheat Germ Agglutinins
pubmed:year
1995
pubmed:articleTitle
Mutation of a conserved amino acid residue (tryptophan 1173) in the tyrosine kinase domain of the IGF-I receptor abolishes autophosphorylation but does not eliminate biologic function.
pubmed:affiliation
Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article