14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization

• Published in: Cellular signalling 2007-11, Vol.19 (11), p.2379-2387
• Main Authors: Tak, Heejae, Jang, Eunsun, Kim, Seung Beom, Park, Jinhwi, Suk, Jinkyu, Yoon, Yoo Sik, Ahn, Jeong Keun, Lee, Jeung-Hoon, Joe, Cheol O.
• Format: Article
• Language: English
• Subjects: 14-3-3 Proteins - metabolism; 14-3-3ɛ; Actin polymerization; Actins - chemistry; Actins - metabolism; Cell migration; Cell Movement - drug effects; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Heat-Shock Proteins - metabolism; HeLa Cells; HSP27; HSP27 Heat-Shock Proteins; Humans; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - metabolism; MAPK; MK5; Models, Biological; Neoplasm Proteins - metabolism; Phosphorylation - drug effects; Protein Binding - drug effects; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; TNFα; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2007.07.016

The signal pathway by which 14-3-3ɛ 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 14-3-3ɛ interacts with MK5. 14-3-3ɛ bound to MK5 inhibits the phosphorylation of HSP27, a known substrate of MK5. Disturbance of actin cytoskeleton organization by 14-3-3ɛ was shown in transfected cells transiently expressing 14-3-3ɛ as well as established cells stably expressing 14-3-3ɛ. Moreover, overexpression of 14-3-3ɛ resulted in the inhibition of cell migration induced by MK5 overexpression or TNFα treatment. Our results suggest that 14-3-3ɛ 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.