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rdf:type |
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lifeskim:mentions |
umls-concept:C0015576,
umls-concept:C0018296,
umls-concept:C0031715,
umls-concept:C0040715,
umls-concept:C0599718,
umls-concept:C0599813,
umls-concept:C0599893,
umls-concept:C0851285,
umls-concept:C1412517,
umls-concept:C1420175,
umls-concept:C1423613,
umls-concept:C1425056,
umls-concept:C1522702,
umls-concept:C1720675,
umls-concept:C2003941
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pubmed:issue |
51
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pubmed:dateCreated |
2008-12-16
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pubmed:abstractText |
Insulin stimulation results in the activation of cyclin-dependent kinase-5 (CDK5) in lipid raft domains via a Fyn-dependent phosphorylation on tyrosine residue 15. In turn, activated CDK5 phosphorylates the Rho family GTP-binding protein TC10alpha on threonine 197 that is sensitive to the CDK5 inhibitor olomoucine and blocked by small interfering RNA-mediated knockdown of CDK5. The phosphorylation deficient mutant T197A-TC10alpha was not phosphorylated and excluded from the lipid raft domain, whereas the phosphorylation mimetic mutant (T197D-TC10alpha) was lipid raft localized. Insulin resulted in the GTP loading of T197D-TC10alpha but not T197A-TC10alpha and in parallel, T197D-TC10alpha but not T197A-TC10alpha depolymerized cortical actin and inhibited insulin-stimulated GLUT4 translocation. These data demonstrate that CDK5-dependent phosphorylation maintains TC10alpha in lipid raft compartments thereby disrupting cortical actin, whereas subsequent dephosphorylation of TC10alpha through inactivation of CDK5 allows for the re-assembly of F-actin. Because cortical actin reorganization is required for insulin-stimulated GLUT4 translocation, these data are consistent with a CDK5-dependent TC10alpha cycling between lipid raft and non-lipid raft compartments.
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fyn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 4,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Kinetin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Rhoq protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Slc2a4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/olomoucine,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:HashimotoKoshiK,
pubmed-author:HisanagaShin-IchiS,
pubmed-author:IzumiTakashiT,
pubmed-author:MoriMasatomoM,
pubmed-author:OhshimaKihachiK,
pubmed-author:OkadaShuichiS,
pubmed-author:PessinJeffrey EJE,
pubmed-author:SaitoTsugumichiT,
pubmed-author:ShimizuHiroyukiH,
pubmed-author:TateiKazuakiK,
pubmed-author:TsuchiyaTakafumiT,
pubmed-author:UeharaYutakaY,
pubmed-author:YamadaEijiroE,
pubmed-author:YamadaMasanobuM,
pubmed-author:YamauchiKeishiK
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35455-63
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18948252-3T3-L1 Cells,
pubmed-meshheading:18948252-Actins,
pubmed-meshheading:18948252-Animals,
pubmed-meshheading:18948252-Cyclin-Dependent Kinase 5,
pubmed-meshheading:18948252-Enzyme Inhibitors,
pubmed-meshheading:18948252-Glucose Transporter Type 4,
pubmed-meshheading:18948252-Insulin,
pubmed-meshheading:18948252-Kinetin,
pubmed-meshheading:18948252-Membrane Microdomains,
pubmed-meshheading:18948252-Mice,
pubmed-meshheading:18948252-Phosphorylation,
pubmed-meshheading:18948252-Protein Transport,
pubmed-meshheading:18948252-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:18948252-RNA, Small Interfering,
pubmed-meshheading:18948252-rho GTP-Binding Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
CDK5-dependent phosphorylation of the Rho family GTPase TC10(alpha) regulates insulin-stimulated GLUT4 translocation.
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pubmed:affiliation |
Department of Medicine, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma 371-0034, Japan. okadash@showa.gunma-u.ac.jp
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pubmed:publicationType |
Journal Article
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