Source:http://linkedlifedata.com/resource/pubmed/id/11579209
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2001-10-1
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| pubmed:abstractText |
PTP1B is a protein tyrosine phosphatase that negatively regulates insulin sensitivity by dephosphorylating the insulin receptor. Akt is a ser/thr kinase effector of insulin signaling that phosphorylates substrates at the consensus motif RXRXXS/T. Interestingly, PTP1B contains this motif (RYRDVS(50)), and wild-type PTP1B (but not mutants with substitutions for Ser(50)) was significantly phosphorylated by Akt in vitro. To determine whether PTP1B is a substrate for Akt in intact cells, NIH-3T3(IR) cells transfected with either wild-type PTP1B or PTP1B-S50A were labeled with [(32)P]-orthophosphate. Insulin stimulation caused a significant increase in phosphorylation of wild-type PTP1B that could be blocked by pretreatment of cells with wortmannin or cotransfection of a dominant inhibitory Akt mutant. Similar results were observed with endogenous PTP1B in untransfected HepG2 cells. Cotransfection of constitutively active Akt caused robust phosphorylation of wild-type PTP1B both in the absence and presence of insulin. By contrast, PTP1B-S50A did not undergo phosphorylation in response to insulin. We tested the functional significance of phosphorylation at Ser(50) by evaluating insulin receptor autophosphorylation in transfected Cos-7 cells. Insulin treatment caused robust receptor autophosphorylation that could be substantially reduced by coexpression of wild-type PTP1B. Similar results were obtained with coexpression of PTP1B-S50A. However, under the same conditions, PTP1B-S50D had an impaired ability to dephosphorylate the insulin receptor. Moreover, cotransfection of constitutively active Akt significantly inhibited the ability of wild-type PTP1B, but not PTP1B-S50A, to dephosphorylate the insulin receptor. We conclude that PTP1B is a novel substrate for Akt and that phosphorylation of PTP1B by Akt at Ser(50) may negatively modulate its phosphatase activity creating a positive feedback mechanism for insulin signaling.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0888-8809
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
15
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1768-80
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:11579209-3T3 Cells,
pubmed-meshheading:11579209-Amino Acid Sequence,
pubmed-meshheading:11579209-Animals,
pubmed-meshheading:11579209-COS Cells,
pubmed-meshheading:11579209-Consensus Sequence,
pubmed-meshheading:11579209-Feedback,
pubmed-meshheading:11579209-Humans,
pubmed-meshheading:11579209-Insulin,
pubmed-meshheading:11579209-Mice,
pubmed-meshheading:11579209-Molecular Sequence Data,
pubmed-meshheading:11579209-Mutation,
pubmed-meshheading:11579209-Phosphorylation,
pubmed-meshheading:11579209-Phosphoserine,
pubmed-meshheading:11579209-Plasmids,
pubmed-meshheading:11579209-Protein Tyrosine Phosphatase, Non-Receptor Type 1,
pubmed-meshheading:11579209-Protein Tyrosine Phosphatases,
pubmed-meshheading:11579209-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11579209-Proto-Oncogene Proteins,
pubmed-meshheading:11579209-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11579209-Receptor, Insulin,
pubmed-meshheading:11579209-Signal Transduction,
pubmed-meshheading:11579209-Transfection
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| pubmed:year |
2001
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| pubmed:articleTitle |
Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor.
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| pubmed:affiliation |
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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| pubmed:publicationType |
Journal Article
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