TY - JOUR
T1 - GANP suppresses the arginine methyltransferase PRMT5 regulating IL-4-mediated STAT6-signaling to IgE production in B cells
AU - Igarashi, Hideya
AU - Kuwahara, Kazuhiko
AU - Yoshida, Mikoto
AU - Xing, Yan
AU - Maeda, Kazuhiko
AU - Nakajima, Koichi
AU - Sakaguchi, Nobuo
N1 - Funding Information:
We thank Drs. N. Araki and A. Irie (Kumamoto University) for their help to determine the amino acid sequence. We also acknowledge technical assistance by H. Nizato and Y. Kawasho, and secretary help of F. Higashi. This work was supported by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, by the grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (N.S.), and by JSPS KAKENHI 17590440 (H.I.). The authors have no conflicting financial interests.
PY - 2009/3
Y1 - 2009/3
N2 - Antigen (Ag)-driven B cells undergo antibody (Ab) affinity maturation and class switching in germinal center (GC) B cells. GANP is one of the molecules required for Ab affinity maturation. We herein found an increase of IgE in B cell ganp-deficient mice and studied the signal transduction pathway regulated by GANP. GANP suppresses the STAT-mediated transcription activity in GC B cells with the regulation of arginine methyltransferase activity by the interaction with JAK-binding protein arginine methyltransferase (PRMT) 5 and JAK1/JAK3 that are responsible for STAT6 activation. The prmt5 mRNA was up-regulated in B cells after stimulation in vitro and in vivo in GC B cells. The loss of GANP caused up-regulation of phosphorylation and arginine dimethylation of STAT6 in B cells after stimulation with LPS and IL-4 in vitro. On the contrary, GANP over-expressed B cells in ganp gene-transgenic mice showed a low STAT6 phosphorylation after stimulation. The over-expression of PRMT5 caused the up-regulation of STAT6-mediated gene transcription, which was also suppressed by the co-transfection of GANP, in luciferase reporter assay. GANP down-regulates JAK1/JAK3 to STAT6-signaling with regulation of arginine methylation activity, which might be responsible for the B cell endogenous suppressive mechanism of hyper-IgE.
AB - Antigen (Ag)-driven B cells undergo antibody (Ab) affinity maturation and class switching in germinal center (GC) B cells. GANP is one of the molecules required for Ab affinity maturation. We herein found an increase of IgE in B cell ganp-deficient mice and studied the signal transduction pathway regulated by GANP. GANP suppresses the STAT-mediated transcription activity in GC B cells with the regulation of arginine methyltransferase activity by the interaction with JAK-binding protein arginine methyltransferase (PRMT) 5 and JAK1/JAK3 that are responsible for STAT6 activation. The prmt5 mRNA was up-regulated in B cells after stimulation in vitro and in vivo in GC B cells. The loss of GANP caused up-regulation of phosphorylation and arginine dimethylation of STAT6 in B cells after stimulation with LPS and IL-4 in vitro. On the contrary, GANP over-expressed B cells in ganp gene-transgenic mice showed a low STAT6 phosphorylation after stimulation. The over-expression of PRMT5 caused the up-regulation of STAT6-mediated gene transcription, which was also suppressed by the co-transfection of GANP, in luciferase reporter assay. GANP down-regulates JAK1/JAK3 to STAT6-signaling with regulation of arginine methylation activity, which might be responsible for the B cell endogenous suppressive mechanism of hyper-IgE.
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U2 - 10.1016/j.molimm.2008.08.272
DO - 10.1016/j.molimm.2008.08.272
M3 - Article
C2 - 19181385
AN - SCOPUS:61449207854
SN - 0161-5890
VL - 46
SP - 1031
EP - 1041
JO - Molecular Immunology
JF - Molecular Immunology
IS - 6
ER -