Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1994-10-21
pubmed:abstractText
SH-PTP2 is a nontransmembrane human protein-tyrosine phosphatase that contains two Src homology 2 (SH2) domains and binds to insulin receptor substrate 1 (IRS-1) via these domains in response to insulin. The expression of a catalytically inactive mutant of SH-PTP2 (containing the mutation Cys-459-->Ser) in Chinese hamster ovary cells that overexpress human insulin receptors (CHO-IR cells) markedly attenuated insulin-stimulated Ras activation. Expression of mutant SH-PTP2 also inhibited MAP kinase activation in response to insulin but not in response to 12-O-tetradecanoyl phorbol-13-acetate. In contrast, the insulin-induced association of phosphoinositide 3-kinase activity with IRS-1 was not affected by the expression of inactive SH-PTP2. Furthermore, the expression of mutant SH-PTP2 had no effect on the binding of Grb2 to IRS-1, on the tyrosine phosphorylation of Shc, or on the formation of the complex between Shc and Grb2 in response to insulin. However, the amount of SH-PTP2 bound to IRS-1 in insulin-treated CHO-IR cells expressing mutant SH-PTP2 was greater than that observed in CHO-IR cells overexpressing wild-type SH-PTP2. Recombinant SH-PTP2 specifically dephosphorylated a synthetic phosphopeptide corresponding to the sequence surrounding Tyr-1172 of IRS-1, a putative binding site for SH-PTP2. Additionally, phenylarsine oxide, an inhibitor of protein-tyrosine phosphatases, inactivated SH-PTP2 in vitro and increased the insulin-induced association of SH-PTP2 with IRS-1. These results suggest that SH-PTP2 may regulate an upstream element necessary for Ras activation in response to insulin and that this upstream element may be required for the Grb2- or Shc-dependent pathway. Furthermore, these results are consistent with the notion that SH-PTP2 may bind to IRS-1 through its SH2 domains in response to insulin and dephosphorylate the phosphotyrosine residue to which it binds, thereby regulating its association with IRS-1.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1280823, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1281790, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1328223, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1334490, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1380456, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1485970, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-15335710, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1623525, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1638629, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1648180, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1650499, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1695146, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1836211, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-1939160, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-2155095, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-2442814, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-2839487, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-3100537, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-3101064, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-3540958, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-6188161, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-6849137, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7504175, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7508445, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7512963, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7681217, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7681589, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7682895, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-7688466, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8096088, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8114695, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8119896, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8128219, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8226787, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8259209, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8264620, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8265614, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8290602, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8294459, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8316835, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8343949, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8388384, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8449939, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8458578, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8491186, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8505282, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8505313, http://linkedlifedata.com/resource/pubmed/commentcorrection/7935386-8514779
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein, http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HRAS protein, human, http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, 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/Oncogene Protein pp60(v-src), 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/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/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins p21(ras), http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6674-82
pubmed:dateRevised
2011-11-17
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