TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase.
BCMA (B cell maturation) is a nonglycosylated integral membrane type I protein that is preferentially expressed in mature B lymphocytes. Previously, we reported in a human malignant myeloma cell line that BCMA is not primarily present on the cell surface but lies in a perinuclear structure that partially overlaps the ... Golgi apparatus. We now show that in transiently or stably transfected cells, BCMA is located on the cell surface, as well as in a perinulear Golgi-like structure. We also show that overexpression of BCMA in 293 cells activates NF-kappa B, Elk-1, the c-Jun N-terminal kinase, and the p38 mitogen-activated protein kinase. Coimmunoprecipitation experiments performed in transfected cells showed that BCMA associates with TNFR-associated factor (TRAF) 1, TRAF2, and TRAF3 adaptor proteins. Analysis of deletion mutants of the intracytoplasmic tail of BCMA showed that the 25-aa protein segment, from position 119 to 143, conserved between mouse and human BCMA, is essential for its association with the TRAFs and the activation of NF-kappa B, Elk-1, and c-Jun N-terminal kinase. BCMA belongs structurally to the TNFR family. Its unique TNFR motif corresponds to a variant motif present in the fourth repeat of the TNFRI molecule. This study confirms that BCMA is a functional member of the TNFR superfamily. Furthermore, as BCMA is lacking a "death domain" and its overexpression activates NF-kappa B and c-Jun N-terminal kinase, we can reasonably hypothesize that upon binding of its corresponding ligand BCMA transduces signals for cell survival and proliferation.
Mesh Terms:
Amino Acid Sequence, Animals, B-Cell Maturation Antigen, B-Lymphocytes, Cell Differentiation, Cell Line, Cell Membrane, Cell Nucleus, Cytoplasm, DNA-Binding Proteins, Enzyme Activation, Genetic Vectors, Humans, Intracellular Fluid, JNK Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinases, Molecular Sequence Data, NF-kappa B, Peptide Mapping, Proteins, Proto-Oncogene Proteins, Receptors, Tumor Necrosis Factor, Sequence Deletion, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 3, Transcription Factors, Tumor Cells, Cultured, ets-Domain Protein Elk-1, p38 Mitogen-Activated Protein Kinases
Amino Acid Sequence, Animals, B-Cell Maturation Antigen, B-Lymphocytes, Cell Differentiation, Cell Line, Cell Membrane, Cell Nucleus, Cytoplasm, DNA-Binding Proteins, Enzyme Activation, Genetic Vectors, Humans, Intracellular Fluid, JNK Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinases, Molecular Sequence Data, NF-kappa B, Peptide Mapping, Proteins, Proto-Oncogene Proteins, Receptors, Tumor Necrosis Factor, Sequence Deletion, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 3, Transcription Factors, Tumor Cells, Cultured, ets-Domain Protein Elk-1, p38 Mitogen-Activated Protein Kinases
J. Immunol.
Date: Aug. 01, 2000
PubMed ID: 10903733
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