Title | Role of zeta PKC in B-cell signaling and function. |
Publication Type | Journal Article |
Year of Publication | 2002 |
Authors | Martin P, Duran A, Minguet S, Gaspar M-L, Diaz-Meco M-T, Rennert P, Leitges M, Moscat J |
Journal | EMBO J |
Volume | 21 |
Issue | 15 |
Pagination | 4049-57 |
Date Published | 2002 Aug 01 |
ISSN | 0261-4189 |
Keywords | Animals, Antibody Formation, Apoptosis, B-Lymphocytes, bcl-X Protein, Cell Division, Enzyme Activation, Gene Expression Regulation, I-kappa B Proteins, Immunity, Cellular, Immunologic Deficiency Syndromes, Interleukin-6, Isoenzymes, Lymphoid Tissue, MAP Kinase Signaling System, Mice, Mice, Knockout, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, NF-kappa B, Protein Kinase C, Proto-Oncogene Proteins c-bcl-2, Receptors, Antigen, B-Cell, T-Lymphocytes, Transcription, Genetic |
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. |
DOI | 10.1093/emboj/cdf407 |
Alternate Journal | EMBO J |
PubMed ID | 12145205 |
PubMed Central ID | PMC126153 |
Related Faculty:
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.