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rdf:type |
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lifeskim:mentions |
umls-concept:C0021641,
umls-concept:C0033684,
umls-concept:C0035820,
umls-concept:C0037083,
umls-concept:C0085409,
umls-concept:C0179586,
umls-concept:C0205224,
umls-concept:C0205225,
umls-concept:C0271510,
umls-concept:C0332281,
umls-concept:C1135629,
umls-concept:C1422073,
umls-concept:C1422760,
umls-concept:C1657858,
umls-concept:C1706092,
umls-concept:C1706433,
umls-concept:C1710082,
umls-concept:C1822704
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pubmed:issue |
20
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pubmed:dateCreated |
2004-5-10
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pubmed:abstractText |
APS (adapter protein with Pleckstrin homology and Src homology 2 domains) is recruited by the autophosphorylated insulin receptor and is essential for Glut4 translocation. Although both APS and CAP (c-Cbl-associated protein) interact with c-Cbl during insulin signaling, the relative importance of each protein in recruiting c-Cbl has not been clear. We performed a side-by-side comparison by ectopic expression of APS or Src homology 2-Balpha (SH2-Balpha) and CAP in Chinese hamster ovary (CHO) cells. In cells co-expressing insulin receptor and CAP, without APS, no association of the insulin receptor and CAP could be detected and no insulin-stimulated phosphorylation of Cbl was observed. Insulin-stimulated Cbl phosphorylation was reconstituted when APS was co-expressed with insulin receptor, with or without CAP. APS or SH2-Balpha and CAP interacted in the basal state, and in the case of APS this interaction was mediated by the C terminus of APS. Insulin stimulation resulted in the dissociation of APS and CAP. Similarly, insulin stimulation also resulted in the dissociation of SH2-Balpha and CAP in CHO cells. CAP was localized to the membrane in the presence of APS. Insulin stimulation resulted in the re-localization of CAP to the cytosol only when APS was co-expressed. In 3T3-L1 adipocytes, small interfering RNA-mediated knockdown of the mouse APS gene abolished the insulin-stimulated phosphorylation of c-Cbl. Taken together, these results indicate that APS plays a central role in recruiting both CAP and c-Cbl to the insulin receptor after insulin stimulation and is necessary and sufficient for the insulin-stimulated phosphorylation of c-Cbl, whereas SH2-Balpha may provide an alternative pathway for the recruitment of CAP.
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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/CBL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cbl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/ponsin
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pubmed:status |
MEDLINE
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pubmed:month |
May
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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 |
14
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21526-32
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15031295-3T3 Cells,
pubmed-meshheading:15031295-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:15031295-Adipocytes,
pubmed-meshheading:15031295-Animals,
pubmed-meshheading:15031295-CHO Cells,
pubmed-meshheading:15031295-Cricetinae,
pubmed-meshheading:15031295-Insulin,
pubmed-meshheading:15031295-Mice,
pubmed-meshheading:15031295-Mice, Knockout,
pubmed-meshheading:15031295-Microfilament Proteins,
pubmed-meshheading:15031295-Phosphotyrosine,
pubmed-meshheading:15031295-Proteins,
pubmed-meshheading:15031295-Proto-Oncogene Proteins,
pubmed-meshheading:15031295-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:15031295-Recombinant Proteins,
pubmed-meshheading:15031295-Transfection,
pubmed-meshheading:15031295-Ubiquitin-Protein Ligases,
pubmed-meshheading:15031295-src Homology Domains
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pubmed:year |
2004
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pubmed:articleTitle |
Primary and essential role of the adaptor protein APS for recruitment of both c-Cbl and its associated protein CAP in insulin signaling.
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pubmed:affiliation |
Institute of Cell Signaling and School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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