Linked Life Data

7906861

Source:http://linkedlifedata.com/resource/pubmed/id/7906861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1994-3-28
pubmed:abstractText
The insulin-dependent tyrosine kinase activity (TKA) of the insulin receptor (IR) plays an essential role in insulin signaling. Thus, dysregulation of IR-TKA might be an important element in the states of insulin resistance. A phosphorylated rat hepatic glycoprotein (pp63) acting as an inhibitor of IR-TK has been described. In search of the human homolog of pp63, we isolated a cDNA clone from a human liver lambda gt11 cDNA library. DNA sequence analysis reveals identity with the mRNA product of a human gene AHSG encoding a serum protein, alpha 2-Heremans Scmid-glycoprotein (alpha 2HSG), with heretofore unknown physiological function. Northern blot analysis demonstrates a 1.8-kilobase mRNA in human liver and HepG2 hepatoma cells. alpha 2HSG, purified from human serum, specifically inhibits insulin-stimulated IR autophosphorylation in vitro and in vivo as well as exogenous substrate tyrosine phosphorylation. alpha 2HSG also inhibits both insulin-induced tyrosine phosphorylation of IRS-1 and the association of IRS-1 with the p85 subunit of phosphatidylinositol-3 kinase in H-35 hepatoma cells. alpha 2HSG inhibits insulin-dependent mitogenesis, but does not affect insulin-stimulated induction of the metabolic enzyme tyrosine aminotransferase. alpha 2HSG does not compete with insulin for binding to IR. Finally, the action of alpha 2HSG is specific toward the IR-TK; its effect does not extend to insulin-like growth factor-I-stimulated TKA. Our results allow us to assign a biochemical function for human alpha 2HSG, namely regulation of insulin action at the IR-TK level.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:geneSymbol
AHSG
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1445-55
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:7906861-Amino Acid Sequence, pubmed-meshheading:7906861-Animals, pubmed-meshheading:7906861-Blood Proteins, pubmed-meshheading:7906861-CHO Cells, pubmed-meshheading:7906861-Cell Division, pubmed-meshheading:7906861-Cricetinae, pubmed-meshheading:7906861-DNA, Complementary, pubmed-meshheading:7906861-Enzyme Induction, pubmed-meshheading:7906861-Glycoproteins, pubmed-meshheading:7906861-Humans, pubmed-meshheading:7906861-L Cells (Cell Line), pubmed-meshheading:7906861-Liver, pubmed-meshheading:7906861-Mice, pubmed-meshheading:7906861-Molecular Sequence Data, pubmed-meshheading:7906861-Phosphorylation, pubmed-meshheading:7906861-Protein Processing, Post-Translational, pubmed-meshheading:7906861-Protein-Tyrosine Kinases, pubmed-meshheading:7906861-Rats, pubmed-meshheading:7906861-Receptor, Insulin, pubmed-meshheading:7906861-Sequence Alignment, pubmed-meshheading:7906861-Sequence Homology, Amino Acid, pubmed-meshheading:7906861-Signal Transduction, pubmed-meshheading:7906861-Tumor Cells, Cultured, pubmed-meshheading:7906861-Tyrosine Transaminase, pubmed-meshheading:7906861-alpha-2-HS-Glycoprotein
pubmed:year
1993
pubmed:articleTitle
Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level.
pubmed:affiliation
Center for Molecular Biology, Wayne State University, Detroit, Michigan 48201.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't