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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
1998-11-17
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pubmed:abstractText |
We identified SH2-Balpha as an insulin-receptor-binding protein based on interaction screening in yeast hybrid systems and co-precipitation in cells. SH2-Balpha contains pleckstrin-homology ('PH') and Src homology 2 (SH2) domains and is closely related to APS (adapter protein with a PH domain and an SH2 domain) and lnk, adapter proteins first identified in lymphocytes. SH2-Balpha is ubiquitously expressed and is present in rat epididymal adipose tissue, liver and skeletal muscle, physiological sites of insulin action. On SDS/PAGE, SH2-Balpha migrates at a molecular mass of 98 kDa, although the predicted size of SH2-Balpha is 79.6 kDa. Insulin causes an electrophoretic mobility shift. SH2-Balpha can be immunoprecipitated using anti-(insulin receptor) antibody from insulin-stimulated cells. Anti-phosphotyrosine antibody or the growth factor receptor-binding protein 2 (Grb2) SH2 domain precipitate SH2-Balpha after insulin stimulation, suggesting that SH2-Balpha is tyrosine-phosphorylated and may be a substrate for the insulin receptor. The SH2-Balpha SH2 domain did not interact with insulin-receptor substrate (IRS) proteins or epidermal-growth-factor receptor. Mutation of the juxtamembrane and C-terminus of the insulin receptor did not abolish the interaction with the SH2 domain. This was further confirmed using a panel of activation-loop single point mutants where mutation of Tyr1158, Tyr1162 and Tyr1163 abolished interaction. Thus SH2-Balpha is a likely component in the insulin-signalling pathway and may function as an alternative signalling protein by interacting with the activation loop of the insulin-receptor cytoplasmic domain.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-2159147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-2449432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-2859121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-3178737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7479769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7486683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7513704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7525547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7537849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7559478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-7935368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8058065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8276809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8524815,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8621530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8622870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8662806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-8798417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9006901,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9062339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9204766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9233773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9312016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9343427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9360986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9369444,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9452421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9742218-9636306
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Aps protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/SH2B1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sh2bpsm1 protein, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
335 ( Pt 1)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
103-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9742218-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:9742218-Animals,
pubmed-meshheading:9742218-Binding Sites,
pubmed-meshheading:9742218-CHO Cells,
pubmed-meshheading:9742218-Carrier Proteins,
pubmed-meshheading:9742218-Cricetinae,
pubmed-meshheading:9742218-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:9742218-Enzyme Activation,
pubmed-meshheading:9742218-GRB2 Adaptor Protein,
pubmed-meshheading:9742218-Protein Binding,
pubmed-meshheading:9742218-Proteins,
pubmed-meshheading:9742218-Rats,
pubmed-meshheading:9742218-Receptor, Insulin,
pubmed-meshheading:9742218-Signal Transduction,
pubmed-meshheading:9742218-src Homology Domains
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pubmed:year |
1998
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pubmed:articleTitle |
SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase.
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pubmed:affiliation |
Cell Signalling Laboratory, Department of Metabolic Medicine, Imperial College School of Medicine-Hammersmith Campus, 150 Du Cane Road, London W12 0NN, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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