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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2003-6-30
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pubmed:abstractText |
Insulin stimulates translocation of glucose transporter isoform type 4 (GLUT4) and the insulin-responsive aminopeptidase (IRAP) from an intracellular storage pool to the plasma membrane in muscle and fat cells. A role for the cytoskeleton in insulin action has been postulated, and the insulin signaling pathway has been well investigated; however, the molecular mechanism by which GLUT4/IRAP-containing vesicles move from an interior location to the cell surface in response to insulin is incompletely understood. Here, we have screened for IRAP-binding proteins using a yeast two-hybrid system and have found that the C-terminal domain of FHOS (formin homolog overexpressed in spleen) interacts with the N-terminal cytoplasmic domain of IRAP. FHOS is a member of the Formin/Diaphanous family of proteins that is expressed most abundantly in skeletal muscle. In addition, there are two novel types of FHOS transcripts generated by alternative mRNA splicing. FHOS78 has a 78-bp insertion and it is expressed mainly in skeletal muscle where it may be the most abundant isoform in humans. The ubiquitously expressed FHOS24 has a 24-bp insertion encoding an in-frame stop codon that results in a truncated polypeptide. It is known that some formin family proteins interact with the actin-binding profilin proteins. Both FHOS and FHOS78 bound to profilin IIa via their formin homology 1 domains, but neither bound profilin I or IIb. Overexpression of FHOS and FHOS78 resulted in enhanced insulin-stimulated glucose uptake in L6 cells to similar levels. However, overexpression of FHOS24, lacking the IRAP-binding domain, did not affect insulin-stimulated glucose uptake. These findings suggest that FHOS mediates an interaction between GLUT4/IRAP-containing vesicles and the cytoskeleton and may participate in exocytosis and/or retention of this membrane compartment.
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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/Aminopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Contractile Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FHOD1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fetal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 4,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Monosaccharide Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PFN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pfn1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pfn2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Profilins,
http://linkedlifedata.com/resource/pubmed/chemical/SLC2A4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Slc2a4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Slc2a4 protein, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1216-29
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12677009-3T3 Cells,
pubmed-meshheading:12677009-Adipocytes,
pubmed-meshheading:12677009-Alternative Splicing,
pubmed-meshheading:12677009-Amino Acid Sequence,
pubmed-meshheading:12677009-Aminopeptidases,
pubmed-meshheading:12677009-Animals,
pubmed-meshheading:12677009-Cells, Cultured,
pubmed-meshheading:12677009-Contractile Proteins,
pubmed-meshheading:12677009-Fetal Proteins,
pubmed-meshheading:12677009-Gene Expression Regulation,
pubmed-meshheading:12677009-Glucose,
pubmed-meshheading:12677009-Glucose Transporter Type 4,
pubmed-meshheading:12677009-Humans,
pubmed-meshheading:12677009-Insulin,
pubmed-meshheading:12677009-Male,
pubmed-meshheading:12677009-Mice,
pubmed-meshheading:12677009-Microfilament Proteins,
pubmed-meshheading:12677009-Molecular Sequence Data,
pubmed-meshheading:12677009-Monosaccharide Transport Proteins,
pubmed-meshheading:12677009-Muscle, Skeletal,
pubmed-meshheading:12677009-Muscle Cells,
pubmed-meshheading:12677009-Muscle Proteins,
pubmed-meshheading:12677009-Nuclear Proteins,
pubmed-meshheading:12677009-Profilins,
pubmed-meshheading:12677009-Protein Structure, Tertiary,
pubmed-meshheading:12677009-Rats,
pubmed-meshheading:12677009-Rats, Sprague-Dawley,
pubmed-meshheading:12677009-Spleen
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pubmed:year |
2003
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pubmed:articleTitle |
The Formin family protein, formin homolog overexpressed in spleen, interacts with the insulin-responsive aminopeptidase and profilin IIa.
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pubmed:affiliation |
Discovery Research Laboratories II, Pharmaceutical Research Division, Takeda Chemical Industries Co., Ltd., Tsukuba, Ibaraki 300-4293, Japan. Tojo_Hideaki@takeda.co.jp
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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