14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization.
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.
Tak
Heejae
H
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Jang
Eunsun
E
Kim
Seung Beom
SB
Park
Jinhwi
J
Suk
Jinkyu
J
Yoon
Yoo Sik
YS
Ahn
Jeong Keun
JK
Lee
Jeung-Hoon
JH
Joe
Cheol O
CO
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
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