Sec8 regulates cytokeratin8 phosphorylation and cell migration by controlling the ERK and p38 MAPK signalling pathways

Toshiaki Tanaka; Mitsuyoshi Iino

doi:10.1016/j.cellsig.2015.02.015

Sec8 regulates cytokeratin8 phosphorylation and cell migration by controlling the ERK and p38 MAPK signalling pathways

Cell Signal. 2015 Jun;27(6):1110-9. doi: 10.1016/j.cellsig.2015.02.015. Epub 2015 Feb 26.

Authors

Toshiaki Tanaka¹, Mitsuyoshi Iino²

Affiliations

¹ 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.
² Department of Dentistry, Oral and Maxillofacial Surgery, Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Japan.

PMID: 25725287
DOI: 10.1016/j.cellsig.2015.02.015

Abstract

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.

Keywords: Cell migration; Cytokeratin8; Sec8; Seven in absentia homologue 1; p21-Activated kinases; p53-Induced RING-H2.

MeSH terms

Cell Movement
Extracellular Signal-Regulated MAP Kinases / metabolism*
Humans
Keratin-8 / metabolism*
MAP Kinase Kinase 1 / metabolism
MAP Kinase Kinase 2 / metabolism
MAP Kinase Kinase 3 / metabolism
MAP Kinase Kinase 6 / metabolism
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Phosphorylation
RNA Interference
RNA, Small Interfering / metabolism
Signal Transduction
Ubiquitin-Protein Ligases / antagonists & inhibitors
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
Vesicular Transport Proteins / antagonists & inhibitors
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism*
p21-Activated Kinases / metabolism
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

EXOC4 protein, human
Keratin-8
Nuclear Proteins
RNA, Small Interfering
Vesicular Transport Proteins
RCHY1 protein, human
Ubiquitin-Protein Ligases
seven in absentia proteins
PAK1 protein, human
PAK2 protein, human
p21-Activated Kinases
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP Kinase Kinase 3
MAP Kinase Kinase 6