Linked Life Data

1317784

Source:http://linkedlifedata.com/resource/pubmed/id/1317784

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-7-6
pubmed:abstractText
To characterize tyrosine kinase activity in signaling ligand/receptor internalization, metabolic labeling and surface radioligand binding were used to follow the processing of both normal and tyrosine kinase-deficient human insulin receptors. The mutant receptor (A/K1018) has an alanine substituted for lysine 1018 in the ATP-binding domain. Rat 1 fibroblasts, expressing either normal human insulin receptors (HIRc) or A/K1018 receptors, were assayed to determine the insulin receptor half-life as well as internalization and down-regulation. Our results show that insulin greatly reduces the half-life of normal insulin receptors (from 9.9 to 5.7 h). The A/K1018 receptor had a much longer half-life (24 h), which was not reduced by the presence of saturating insulin concentrations. The A/K1018 receptor does not undergo down-regulation after long term insulin exposure, while HIRc cells showed a 34% decrease in insulin receptor number. This down-regulation is accounted for by the accelerated turnover rate of normal receptors in the presence of insulin. To confirm that the kinase activity is necessary for normal endocytosis, we also show that ATP depletion in HIRc cells resulted in significant decreases in receptor internalization and that tyrosine kinase-defective receptors also fail to internalize in a different cell type (rat Fao hepatocytes). Lastly, the complement of normal rat insulin receptors in cells expressing the kinase-defective receptors endocytose normally. We conclude that the defect in endocytosis observed in kinase-defective receptors is intrinsic to this receptor and not due to a dominant inhibitory effect on cellular endocytotic machinery.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3441-52
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Tyrosine kinase-defective insulin receptors undergo decreased endocytosis but do not affect internalization of normal endogenous insulin receptors.
pubmed:affiliation
Department of Medicine, University of California-San Diego, La Jolla 92093.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.