| First Author | Igarashi H | Year | 2009 |
| Journal | Mol Immunol | Volume | 46 |
| Issue | 6 | Pages | 1031-41 |
| PubMed ID | 19181385 | Mgi Jnum | J:146863 |
| Mgi Id | MGI:3838691 | Doi | 10.1016/j.molimm.2008.08.272 |
| Citation | Igarashi H, et al. (2009) GANP suppresses the arginine methyltransferase PRMT5 regulating IL-4-mediated STAT6-signaling to IgE production in B cells. Mol Immunol 46(6):1031-41 |
| abstractText | 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. |
