Source:http://linkedlifedata.com/resource/pubmed/id/15924411
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
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| pubmed:dateCreated |
2005-5-31
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| pubmed:databankReference | |
| pubmed:abstractText |
Recently we have shown that insulin fails to induce the phosphorylation of IRS-1 in the retina [Rajala et al. (2004) Biochemistry 43, 5637-5650], even though there is widespread expression of IRS-1 throughout the retina. These results suggest the expression of tissue-specific regulators in the retina. Yeast two-hybrid screening of a bovine retinal cDNA library with the cytoplasmic domain of retinal insulin receptor identified a novel member of the Grb7 gene family, Grb14. Phosphorylation prediction software indicated 6 out of 18 tyrosine residues were most likely to be phosphorylated. Out of six tyrosine phosphorylation sites, one of the tyrosine residues in Grb14 is present in a conserved sequence motif, FXNPXY. The NPXY motifs are recognized by proteins containing a domain known as phosphotyrosine-binding (PTB) or phosphotyrosine-interacting domain (PID). The biological function of the PTB domain is to drive recruitment of signaling adapters such as IRS-1 or Shc to NPXpY (pY stands for phosphotyrosine) on activated receptor tyrosine kinases. We have made a novel finding that the PTB domain of IRS-1 binds to the NPXY motif of Grb14 in a phosphorylation-independent manner. In addition, Grb14-IRS-1 complexes are detected in lysates prepared from retina tissues. We suggest that the Grb14 NPXY motif could be acting as a dominant negative for IRS-1 functions in the retina, and this hypothesis is consistent with the recent study that Grb14-deficient mice exhibit enhanced IRS-1 phosphorylation and activation of protein kinase B. This is the first report describing the presence of the NPXY motif in Grb14 and binding of the PTB domain of IRS-1 in a phosphorylation-independent manner.
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRS2 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, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
7
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| pubmed:volume |
44
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7929-35
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:15924411-Amino Acid Motifs,
pubmed-meshheading:15924411-Amino Acid Sequence,
pubmed-meshheading:15924411-Animals,
pubmed-meshheading:15924411-Carrier Proteins,
pubmed-meshheading:15924411-Cattle,
pubmed-meshheading:15924411-Glutathione Transferase,
pubmed-meshheading:15924411-Humans,
pubmed-meshheading:15924411-Insulin Receptor Substrate Proteins,
pubmed-meshheading:15924411-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15924411-Molecular Sequence Data,
pubmed-meshheading:15924411-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15924411-Phosphoproteins,
pubmed-meshheading:15924411-Phosphorylation,
pubmed-meshheading:15924411-Phosphotyrosine,
pubmed-meshheading:15924411-Protein Structure, Tertiary,
pubmed-meshheading:15924411-Protein Subunits,
pubmed-meshheading:15924411-Receptor, Insulin,
pubmed-meshheading:15924411-Retina,
pubmed-meshheading:15924411-src Homology Domains
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| pubmed:year |
2005
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| pubmed:articleTitle |
Identification of a NPXY motif in growth factor receptor-bound protein 14 (Grb14) and its interaction with the phosphotyrosine-binding (PTB) domain of IRS-1.
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| pubmed:affiliation |
Department of Cell Biology, University of Oklahoma Health Sciences Center, and Dean A. McGee Eye Institute, Oklahoma City, Oklahoma 73104, USA. raju-rajala@ouhsc.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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