title: Regulation of cofilin activity by CaMKII and calcineurin.
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.
authors.affiliation: Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Jian-Wu
authors.initials: JW
authors.lastname: Zhao
authors.forename: Zhong-Li
authors.initials: ZL
authors.lastname: Gao
authors.forename: Qiu-Ye
authors.initials: QY
authors.lastname: Ji
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Han-Yang
authors.initials: HY
authors.lastname: Zhang
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Yang
authors.forename: Feng-juan
authors.initials: FJ
authors.lastname: Xing
authors.forename: Ling-jie
authors.initials: LJ
authors.lastname: Meng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D061207:Calcium Ionophores / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D051338:Cofilin 1 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D054461:Lim Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D048948:14-3-3 Proteins; C495810:CFL1 protein, human; D061207:Calcium Ionophores; D051338:Cofilin 1; D011994:Recombinant Proteins; D000001:Calcimycin; D012694:Serine; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human; D002118:Calcium