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

J Immunol. 2000 Aug 1;165(3):1322-30. doi: 10.4049/jimmunol.165.3.1322.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Cell Maturation Antigen
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / immunology
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Nucleus / immunology
  • Cell Nucleus / metabolism
  • Cytoplasm / immunology
  • Cytoplasm / metabolism
  • DNA-Binding Proteins*
  • Enzyme Activation / immunology
  • Genetic Vectors / pharmacology
  • Humans
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System / immunology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Peptide Mapping
  • Proteins / genetics
  • Proteins / metabolism
  • Proteins / physiology
  • Proto-Oncogene Proteins / metabolism*
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / physiology
  • 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

Substances

  • B-Cell Maturation Antigen
  • DNA-Binding Proteins
  • ELK1 protein, human
  • Elk1 protein, mouse
  • NF-kappa B
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 3
  • TNFRSF17 protein, human
  • Tnfrsf17 protein, mouse
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases