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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
1994-6-30
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pubmed:abstractText |
The phosphotyrosine (Tyr(P)) form of insulin receptor substrate 1 (IRS-1) is a key component in insulin signaling. Our previous study revealed that Tyr(P) IRS-1 binds to the widely distributed tyrosine phosphatase PTP2C through the src homology 2 (SH2) domains of the latter. In the present study, we examined the activity of this enzyme and of a truncated form lacking the SH2 domains (delta PTP2C) toward IRS-1 and also toward the cytoplasmic domain of the insulin receptor. Tyr(P) IRS-1 was prepared by phosphorylation of recombinant IRS-1 with recombinant cytoplasmic insulin receptor kinase (CIRK). PTP2C rapidly dephosphorylated Tyr(P) IRS-1; dephosphorylation by delta PTP2C was approximately one-third as fast. Other substrates, including Tyr(P) CIRK, were not dephosphorylated as rapidly by PTP2C; moreover, delta PTP2C was at least 10 times more active than PTP2C toward CIRK and other substrates. These results indicate that the binding of Tyr(P) residues on IRS-1 to the SH2 domain(s) of PTP2C enhances its activity toward IRS-1 and suggest that PTP2C is the phosphatase responsible for the dephosphorylation of IRS-1 in vivo. In addition, with the expectation that a PTP2C-resistant form of IRS-1 will be useful in investigations of IRS-1 function, we determined that IRS-1 can be thiophosphorylated with adenosine 5'-O-(3-thiotriphosphate) and CIRK and that this form of IRS-1 is resistant to PTP2C.
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pubmed:grant |
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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/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SH2 Domain-Containing Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15833-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7515062-Animals,
pubmed-meshheading:7515062-Humans,
pubmed-meshheading:7515062-Insulin Receptor Substrate Proteins,
pubmed-meshheading:7515062-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:7515062-Kinetics,
pubmed-meshheading:7515062-Moths,
pubmed-meshheading:7515062-Phosphoproteins,
pubmed-meshheading:7515062-Phosphorylation,
pubmed-meshheading:7515062-Phosphotyrosine,
pubmed-meshheading:7515062-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:7515062-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:7515062-Protein Tyrosine Phosphatases,
pubmed-meshheading:7515062-Rats,
pubmed-meshheading:7515062-Receptor, Insulin,
pubmed-meshheading:7515062-Recombinant Proteins,
pubmed-meshheading:7515062-SH2 Domain-Containing Protein Tyrosine Phosphatases,
pubmed-meshheading:7515062-Substrate Specificity,
pubmed-meshheading:7515062-Transfection,
pubmed-meshheading:7515062-Tyrosine
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pubmed:year |
1994
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pubmed:articleTitle |
Dephosphorylation of insulin receptor substrate 1 by the tyrosine phosphatase PTP2C.
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pubmed:affiliation |
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755.
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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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