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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
1987-5-6
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pubmed:abstractText |
Three major functional characteristics of the insulin receptor are negative cooperativity, down-regulation, and beta-subunit tyrosine kinase activity. To investigate the inter-relationships among these functions we studied four antibodies to the insulin receptor alpha-subunit. These monoclonal antibodies competitively inhibited 125I-insulin binding to the insulin receptor of human IM-9 and HEP-G2 cells. When the antibodies were radiolabeled, insulin competed strongly with two antibodies (MA-10 and MA-51) for binding to the insulin receptor, but competed weakly with the two others (MA-5 and MA-20). Antibodies MA-10 and MA-51, like insulin, accelerated the dissociation of bound 125I-insulin from receptors; in contrast, MA-5 and MA-20 strongly inhibited 125I-insulin dissociation. Antibodies MA-10 and MA-51 induced down-regulation of insulin receptors with a potency similar to that of insulin. In contrast, MA-5 and MA-20 were more potent than insulin. None of the antibodies either alone or in combination influenced autophosphorylation of the insulin receptor beta-subunit. These data indicate, therefore, that two major epitopes can be identified on the alpha-subunit of the insulin receptor by the use of monoclonal antibodies. One epitope, recognized by antibodies MA-10 and MA-51, is close to or near the insulin-binding site and mimics insulin-induced negative cooperatively and down-regulation. The other epitope, recognized by antibodies MA-5 and MA-20, is at some distance from the insulin-binding site, and only mimics down-regulation. These data suggest, therefore, that: negative cooperativity and down-regulation may not be inter-related and both processes are independent of insulin receptor tyrosine kinase activity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
262
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4134-40
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:2435731-Antibodies, Monoclonal,
pubmed-meshheading:2435731-Binding, Competitive,
pubmed-meshheading:2435731-Carcinoma, Hepatocellular,
pubmed-meshheading:2435731-Cell Line,
pubmed-meshheading:2435731-Cell Membrane,
pubmed-meshheading:2435731-Epitopes,
pubmed-meshheading:2435731-Female,
pubmed-meshheading:2435731-Humans,
pubmed-meshheading:2435731-Immunosorbent Techniques,
pubmed-meshheading:2435731-Insulin,
pubmed-meshheading:2435731-Liver Neoplasms,
pubmed-meshheading:2435731-Lymphocytes,
pubmed-meshheading:2435731-Phosphorylation,
pubmed-meshheading:2435731-Placenta,
pubmed-meshheading:2435731-Pregnancy,
pubmed-meshheading:2435731-Protein-Tyrosine Kinases,
pubmed-meshheading:2435731-Receptor, Insulin
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pubmed:year |
1987
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pubmed:articleTitle |
Effect of monoclonal antibodies on human insulin receptor autophosphorylation, negative cooperativity, and down-regulation.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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