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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1996-12-17
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pubmed:abstractText |
Rat-1 fibroblasts overexpressing the human insulin receptor undergo rapid actin rearrangement in response to insulin. Breakdown of stress fibers present in quiescent cells is followed by transient membrane ruffling and a return of stress fibers. We investigated the signaling pathways that mediate this insulin-stimulated reorganization of the actin cytoskeleton, which was visualized with rhodamine-phalloidin. Treatment of cells with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin prevented insulin action at the preliminary step of stress fiber breakdown. Cellular microinjection of a polyclonal antibody directed against the p85 subunit of PI3-kinase as well as a purified recombinant p85-SH2 domain protein also inhibited actin reorganization. Transient expression of a constitutively active form of PI3-kinase (p110*) was sufficient to cause both stress fiber breakdown and membrane ruffling in the absence of insulin. Microinjection of a polyclonal anti-Shc antibody or dominant negative N17-Ras protein did not affect actin dynamics, and although constitutively active V12-Ras caused modest cytoskeletal reorganization, this effect was blocked by pretreatment with wortmannin. In summary, activation of PI3-kinase is necessary and sufficient to stimulate actin rearrangement, indicating that PI3-kinase may initiate the only signaling cascade required for insulin to induce cytoskeletal restructuring.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0013-7227
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
137
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5045-54
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:8895379-Actins,
pubmed-meshheading:8895379-Androstadienes,
pubmed-meshheading:8895379-Animals,
pubmed-meshheading:8895379-Cell Division,
pubmed-meshheading:8895379-Cell Line,
pubmed-meshheading:8895379-Cytoskeleton,
pubmed-meshheading:8895379-Enzyme Inhibitors,
pubmed-meshheading:8895379-Epidermal Growth Factor,
pubmed-meshheading:8895379-Fibroblasts,
pubmed-meshheading:8895379-Humans,
pubmed-meshheading:8895379-Insulin,
pubmed-meshheading:8895379-Kinetics,
pubmed-meshheading:8895379-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:8895379-Phosphoproteins,
pubmed-meshheading:8895379-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:8895379-Phosphotyrosine,
pubmed-meshheading:8895379-Rats,
pubmed-meshheading:8895379-Receptor, Insulin,
pubmed-meshheading:8895379-Recombinant Proteins,
pubmed-meshheading:8895379-Stress, Mechanical,
pubmed-meshheading:8895379-Transfection
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pubmed:year |
1996
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pubmed:articleTitle |
Phosphatidylinositol 3-kinase is necessary and sufficient for insulin-stimulated stress fiber breakdown.
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pubmed:affiliation |
Department of Medicine, Veterans Administration Medical Center, University of California-San Diego, La Jolla 92093, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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