Abstract
We have previously reported the physical interaction between Daxx, the adaptor protein that mediates activation of the Jun amino-terminal kinase (JNK), and GLUT4, the insulin-dependent glucose transporter, interaction that involves their C-domains. Co-immunoprecipitation and two-hybrid-based protein-protein interaction studies show now that Daxx and GLUT4 interact with JNK1 through D-sites in their NH(2)-(aa 1-501) and large endofacial loop, respectively. Serum deprivation strongly enhances the association of JNK1 with Daxx and dissociates the kinase from GLUT4. SP600125, a potent JNK1 inhibitor, reduces the JNK1 activity associated with GLUT4 and the phosphorylation of two minor GLUT4 species in serum-starved 3T3-L1 adipocytes. In addition, Daxx interacts with kinesin KIF5B through the 6xTPR domain of the kinesin light chain, a domain engaged in the grab hold of protein cargo by kinesin motors that codistribute with JNK. Depletion of Daxx in 3T3-L1 adipocytes provokes the partial translocation of the GLUT4 retained in the GLUT4 storage compartment to endosomes.
(c) 2008 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipocytes / drug effects
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Adipocytes / enzymology
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Animals
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Anthracenes / pharmacology
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Co-Repressor Proteins
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Glucose Transporter Type 4 / chemistry
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Glucose Transporter Type 4 / metabolism*
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Humans
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Immunoprecipitation
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Insulin Receptor Substrate Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kinesins / metabolism*
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Mice
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Microtubules / drug effects
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Microtubules / metabolism
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Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 8 / chemistry
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Mitogen-Activated Protein Kinase 8 / metabolism*
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Molecular Chaperones
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism*
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Phosphorylation / drug effects
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Protein Binding / drug effects
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Protein Transport / drug effects
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Rats
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Serum
Substances
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Anthracenes
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Carrier Proteins
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Co-Repressor Proteins
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Daxx protein, mouse
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Glucose Transporter Type 4
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Insulin Receptor Substrate Proteins
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Intracellular Signaling Peptides and Proteins
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Irs1 protein, mouse
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Molecular Chaperones
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Nuclear Proteins
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pyrazolanthrone
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Mitogen-Activated Protein Kinase 8
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Kif5b protein, mouse
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Kinesins