Abstract
The signal pathway by which 14-3-3epsilon inhibits cell migration induced by MAPK-activated protein kinase 5 (MK5) was investigated in cultured HeLa cells. Both in vivo and in vitro analyses have revealed that 14-3-3epsilon interacts with MK5. 14-3-3epsilon bound to MK5 inhibits the phosphorylation of HSP27, a known substrate of MK5. Disturbance of actin cytoskeleton organization by 14-3-3epsilon was shown in transfected cells transiently expressing 14-3-3epsilon as well as established cells stably expressing 14-3-3epsilon. Moreover, overexpression of 14-3-3epsilon resulted in the inhibition of cell migration induced by MK5 overexpression or TNFalpha treatment. Our results suggest that 14-3-3epsilon bound to MK5 inhibits cell migration by inhibiting the phosphorylation of HSP27 whose phosphorylation regulates F-actin polymerization, actin cytoskeleton organization and subsequent actinfilament dynamics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins / metabolism*
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Actins / chemistry*
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Actins / metabolism*
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Cell Movement* / drug effects
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Cytoskeleton / drug effects
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Cytoskeleton / metabolism
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HSP27 Heat-Shock Proteins
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HeLa Cells
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Heat-Shock Proteins / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / metabolism*
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Models, Biological
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Molecular Chaperones
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Neoplasm Proteins / metabolism
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Phosphorylation / drug effects
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Protein Binding / drug effects
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / metabolism*
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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14-3-3 Proteins
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Actins
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HSP27 Heat-Shock Proteins
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HSPB1 protein, human
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Heat-Shock Proteins
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Intracellular Signaling Peptides and Proteins
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Molecular Chaperones
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Neoplasm Proteins
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Tumor Necrosis Factor-alpha
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YWHAE protein, human
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MAP-kinase-activated kinase 5
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Protein Serine-Threonine Kinases