title: 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization.
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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
authors.forename: Heejae
authors.initials: H
authors.lastname: Tak
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jang
authors.forename: Seung Beom
authors.initials: SB
authors.lastname: Kim
authors.forename: Jinhwi
authors.initials: J
authors.lastname: Park
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Suk
authors.forename: Yoo Sik
authors.initials: YS
authors.lastname: Yoon
authors.forename: Jeong Keun
authors.initials: JK
authors.lastname: Ahn
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Cheol O
authors.initials: CO
authors.lastname: Joe
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D048948:14-3-3 Proteins; D000199:Actins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; C482983:YWHAE protein, human; C111049:MAP-kinase-activated kinase 5; D017346:Protein Serine-Threonine Kinases