Casein kinase 2 phosphorylates and stabilizes C/EBPβ in pancreatic β cells

• Published in: Biochemical and biophysical research communications 2018-02, Vol.497 (1), p.451-456
• Main Authors: Takai, Tomoko, Matsuda, Tomokazu, Matsuura, Yuki, Inoue, Kaho, Suzuki, Emi, Kanno, Ayumi, Kimura-Koyanagi, Maki, Asahara, Shun-ichiro, Hatano, Naoya, Ogawa, Wataru, Kido, Yoshiaki
• Format: Article
• Language: English
• Subjects: Casein kinase 2 (CK2); CCAAT/Enhancer-binding protein β (C/EBPβ); Endoplasmic reticulum stress; Pancreatic β cell failure
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.02.108

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to pancreatic β cell failure. CCAAT/enhancer-binding protein (C/EBP) β is highly induced by ER stress and AMP-activated protein kinase (AMPK) suppression in pancreatic β cells, and its accumulation reduces pancreatic β cell mass. We investigated the phosphorylation state of C/EBPβ under these conditions. Casein kinase 2 (CK2) was found to co-localize with C/EBPβ in MIN6 cells. It phosphorylated S222 of C/EBPβ, a previously unidentified phosphorylation site. We found that C/EBPβ is phosphorylated by CK2 under AMPK suppression and ER stress, which are important from the viewpoint of the worsening pathological condition of type 2 diabetes, such as decreased insulin secretion and apoptosis of pancreatic β cells. •C/EBPβ is accumulated in pancreatic β cells under reduced pf AMPK activity.•Serine residue at position 222 of C/EBPβ is phosphorylated under AMPK suppression.•Casein kinase 2 (CK2) and C/EBPβ co-localized in the nucleus.•CK2 binds to and phosphorylates C/EBPβ directly.