Abstract
Cofilin promotes actin filament turnover by severing and depolymerizing actin filaments. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase1 (LIMK1) and is activated when protein phosphatase Slingshot-1L (SSH1L) dephosphorylates this residue. The authors have shown that Ca-induced cofilin dephosphorylation is mediated by calcineurin (Cn)-dependent activation of SSH1L. In this study, Ca/calmodulin-dependent protein kinase II (CaMKII) is shown to negatively regulate SSH1L activity and bind to SSH1L in a complex with 14-3-3. Phosphorylation of LIMK1 by CaMKII and its subsequent activation regulates the subcellular localization of SSH1L. Based on these findings, the authors suggest that CaMKII and Cn provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization.
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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Actin Cytoskeleton / chemistry
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Actin Cytoskeleton / metabolism
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Calcimycin / pharmacology
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Calcineurin / metabolism*
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Calcium / metabolism
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Calcium Ionophores / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
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Cofilin 1 / metabolism*
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Enzyme Activation / drug effects
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Gene Knockdown Techniques
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HEK293 Cells
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Humans
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Lim Kinases / antagonists & inhibitors
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Lim Kinases / genetics
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Lim Kinases / metabolism
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MCF-7 Cells
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Models, Biological
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism
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Phosphorylation
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Protein Binding
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Serine / chemistry
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Signal Transduction
Substances
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14-3-3 Proteins
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CFL1 protein, human
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Calcium Ionophores
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Cofilin 1
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Recombinant Proteins
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Calcimycin
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Serine
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LIMK1 protein, human
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Lim Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcineurin
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Phosphoprotein Phosphatases
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SSH1 protein, human
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Calcium