Role of ζPKC in B-cell signaling and function

The atypical protein kinase C isoform, zetaPKC, has been implicated in the control of extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-kappaB pathways. Recent evidence from zetaPKC knock-out mice demonstrates that this kinase is important for NF-kappaB transcriptional activity but not for ERK activation in embryonic fibroblasts. The lack of zetaPKC produces in mice a number of alterations in the development of secondary lymphoid tissues that could be accounted for, at least in part, by defects in B-cell function. Here, we present evidence that the loss of zetaPKC selectively impairs signaling through the B-cell receptor, resulting in inhibition of cell proliferation and survival, as well as defects in the activation of ERK and the transcription of NF-kappaB-dependent genes. Furthermore, zetaPKC-/- mice are unable to mount an optimal T-cell-dependent immune response. Collectively, these results genetically establish a critical role for zetaPKC in B-cell function in vitro and in vivo.