| First Author | Khan N | Year | 2021 |
| Journal | J Immunol | Volume | 207 |
| Issue | 9 | Pages | 2288-2296 |
| PubMed ID | 34588218 | Mgi Jnum | J:329531 |
| Mgi Id | MGI:6849696 | Doi | 10.4049/jimmunol.2100295 |
| Citation | Khan N, et al. (2021) Signal Integration by Translocation and Phosphorylation of PKCdelta in the B Cell Alternate Pathway. J Immunol 207(9):2288-2296 |
| abstractText | B cell signaling for activation via the BCR occurs as an isolated event only in vitro; in real life, BCR signaling takes place within a complex milieu that involves interactions with agents that trigger additional receptors. Chief among these is IL-4. We have shown that BCR signaling is reprogrammed by IL-4 receptor engagement and that this reprogramming involves creation of a new, signalosome-independent, Lyn-dependent alternate signaling pathway in B cells isolated from BALB/cByJ mice. A unique aspect of the alternate pathway is protein kinase Cdelta (PKCdelta) phosphorylation. In dissecting this pathway, we unexpectedly found that Lyn is associated with IL-4Ralpha, that IL-4 induces Lyn activation, and that Lyn immunoprecipitated from IL-4-treated B cells capably phosphorylates PKCdelta in a cell-free system. However, PKCdelta phosphorylation does not occur in the absence of BCR triggering in vivo. This raised the question of why IL-4 alone failed to produce PKCdelta phosphorylation. We considered the possibility that Lyn and PKCdelta may be spatially separated. As expected, before any treatment, Lyn is located primarily in the membrane fraction, whereas PKCdelta is located mainly in the cytosol fraction. However, when anti-Ig follows IL-4 treatment, PKCdelta is found in the membrane fraction and phosphorylated. This translocation of PKCdelta to the membrane fraction is not affected by loss of Lyn, although PKCdelta phosphorylation requires Lyn. Thus, PKCdelta phosphorylation through the alternate pathway represents the result of signal integration, whereby neither IL-4 nor anti-Ig working alone produces this outcome, but together they achieve this result by Lyn activation (IL-4) and PKCdelta translocation (IL-4 followed by anti-Ig). |
