| First Author | Guo B | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 6 | Pages | 1643-50 |
| PubMed ID | 23457006 | Mgi Jnum | J:198141 |
| Mgi Id | MGI:5495585 | Doi | 10.1002/eji.201242830 |
| Citation | Guo B, et al. (2013) A novel Lyn-protein kinase Cdelta/epsilon-protein kinase D axis is activated in B cells by signalosome-independent alternate pathway BCR signaling. Eur J Immunol 43(6):1643-50 |
| abstractText | BCR signaling initiates multiple activities critical for B-cell function. Recently, we identified an alternate BCR signaling pathway, induced by IL-4, that is signalosome-independent, unlike the classical signalosome-dependent pathway, and that leads to activation of the MAP kinase, ERK. Here we questioned whether alternate pathway signaling extends to other key downstream events, especially protein kinase D (PKD) activation. We found that in murine spleen-derived B cells the IL-4-induced alternate pathway for BCR signaling results in PKD and PKD substrate phosphorylation, and that alternate pathway phosphorylation of HDAC5/7 and other key substrates requires PKD. Furthermore, we found that tyrosine phosphorylation of PKCdelta/epsilon occurs as a result of alternate but not classical pathway signaling and is required for phosphorylation of PKD and PKD substrates. This result identifies PKCdelta/epsilon tyrosine phosphorylation as a unique outcome of the alternate pathway. The alternate pathway is mediated by Lyn that is not required for classical pathway signaling and we found that Lyn associates directly with PKCdelta/epsilon and is required for phosphorylation of PKCdelta/epsilon and of PKD. These findings indicate that IL-4 influences B-cell activation by inducing a novel signaling pathway from BCR to Lyn to PKCdelta/epsilon to PKD. |
