Abstract
The atypical protein kinase C isoform, zeta PKC, has been implicated in the control of extracellular signal-regulated kinase (ERK) and nuclear factor (NF)-kappa B pathways. Recent evidence from zeta PKC knock-out mice demonstrates that this kinase is important for NF-kappa B transcriptional activity but not for ERK activation in embryonic fibroblasts. The lack of zeta PKC 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 zeta PKC 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-kappa B-dependent genes. Furthermore, zeta PKC-/- mice are unable to mount an optimal T-cell-dependent immune response. Collectively, these results genetically establish a critical role for zeta PKC in B-cell function in vitro and in vivo.