Sec8 regulates cytokeratin8 phosphorylation and cell migration by controlling the ERK and p38 MAPK signalling pathways.
Cell migration is involved in numerous biological processes, including morphogenesis, wound healing and inflammatory responses, and is regulated by harmonic modulations of cellular cytoskeletal elements. The intermediate filament cytokeratin8 is one cytoskeletal element that has been implicated in cell migration. Sec8 is a component of an exocyst complex and is associated with various phenomena, such as cell migration, invadopodia formation, cytokinesis, glucose uptake and neural development. However, the relationship between Sec8 and cytokeratin8 remains to be elucidated. In this study, depleting Sec8 in HSC3 cells suppressed their migration by controlling the phosphorylation of cytokeratin8 at Ser73. This reduced cytokeratin8 phosphorylation at Ser73 is regulated by the activation of ERK and p38 mitogen-activated protein kinases (MAPK) signalling pathways via the downregulation of p21-activated kinases by p53-induced RING-H2 (Pirh2) and seven-in-absentia homologue 1 (Siah1) under conditions of Sec8 knockdown.
Department of Anatomy and Cell Biology, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan; Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan. Electronic address: ttanaka@med.id.yamagata-u.ac.jp.
Toshiaki
T
Tanaka
Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.
Mitsuyoshi
M
Iino
D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D053533:Keratin-8 / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D048371:MAP Kinase Kinase 3 / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
C489607:EXOC4 protein, human; D053533:Keratin-8; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; C515903:PAK1 protein, human; C515907:PAK2 protein, human; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6
Cell migration; Cytokeratin8; Sec8; Seven in absentia homologue 1; p21-Activated kinases; p53-Induced RING-H2