Role of zeta PKC in B-cell signaling and function.
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.
Martin
Pilar
P
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autonoma de Madrid, Canto Blanco, E-28049 Madrid, Spain.
Duran
Angeles
A
Minguet
Susana
S
Gaspar
María-Luisa
ML
Diaz-Meco
Maria-Teresa
MT
Rennert
Paul
P
Leitges
Michael
M
Moscat
Jorge
J
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology; D020672:I-kappa B Proteins / Q000502:physiology; D007111:Immunity, Cellular / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008221:Lymphoid Tissue / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014158:Transcription, Genetic / Q000502:physiology; D051020:bcl-X Protein; D000099221:Protein Kinase C zeta
D020672:I-kappa B Proteins; D015850:Interleukin-6; D007527:Isoenzymes; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D011493:Protein Kinase C; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D051020:bcl-X Protein; D000099221:Protein Kinase C zeta; C494812:Bcl2l1 protein, mouse