Serum starvation activates NF-κB through G protein β2 subunit-mediated signal.
Several cell stresses induce nuclear factor-kappaB (NF-κB) activation, which include irradiation, oxidation, and UV. Interestingly, serum-starving stress-induced NF-κB activation in COS cells, but not in COS-A717 cells. COS-A717 is a mutant cell line of COS cells that is defective of the NF-κB signaling pathway. We isolated genes with compensating activity for the NF-κB pathway and one gene encoded the G protein β2 (Gβ2). Gβ2 is one of the G protein-coupled receptor signaling effectors. In COS-A717 cells, Gβ2 expression is significantly reduced. In Gβ2 cDNA-transfected COS-A717 cells, the NF-κB activity was increased along with the recovery of Gβ2 expression. Furthermore, serum-starving stress induced the NF-κB activity in Gβ2-transfected COS-A717 cells. Consistently, the serum-starved COS cells with siRNA-reduced Gβ2 protein expression showed decreased NF-κB activity. These results indicate that Gβ2 is required for starvation-induced NF-κB activation and constitutive NF-κB activity. We propose that serum contains some molecule(s) that strongly inhibits NF-κB activation mediated through Gβ2 signaling.
Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Tomoko
T
Kohno
Yoshinao
Y
Kubo
Kiyoshi
K
Yasui
Megumi
M
Haraguchi
Sayuri
S
Shigematsu
Koon Jiew
KJ
Chua
Toshifumi
T
Matsuyama
Hideki
H
Hayashi
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*
D016895:Culture Media, Serum-Free; D044387:GTP-Binding Protein beta Subunits; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase