Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS

Y Wu; D Bressette; J A Carrell; T Kaufman; P Feng; K Taylor; Y Gan; Y H Cho; A D Garcia; E Gollatz; D Dimke; D LaFleur; T S Migone; B Nardelli; P Wei; S M Ruben; S J Ullrich; H S Olsen; P Kanakaraj; P A Moore; K P Baker

doi:10.1074/jbc.M005224200

Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS

J Biol Chem. 2000 Nov 10;275(45):35478-85. doi: 10.1074/jbc.M005224200.

Authors

Affiliation

¹ Department of Molecular Biology, Human Genome Sciences, Inc., Rockville, Maryland 20850, USA.

PMID: 10956646
DOI: 10.1074/jbc.M005224200

Abstract

An expression cloning approach was employed to identify the receptor for B-lymphocyte stimulator (BLyS) and identified the tumor necrosis factor receptor superfamily member TACI as a BLyS-binding protein. Expression of TACI in HEK293T cells confers on the cells the ability to bind BLyS with subnanomolar affinity. Furthermore, a TACI-Fc fusion protein recognizes both the cleaved, soluble form of BLyS as well as the membrane BLyS present on the cell surface of a recombinant cell line. TACI mRNA is found predominantly in B-cells and correlates with BLyS binding in a panel of B-cell lines. We also demonstrate that TACI interacts with nanomolar affinity with the BLyS-related tumor necrosis factor homologue APRIL for which no clear in vivo role has been described. BLyS and APRIL are capable of signaling through TACI to mediate NF-kappaB responses in HEK293 cells. We conclude that TACI is a receptor for BLyS and APRIL and discuss the implications for B-cell biology.

MeSH terms

B-Cell Activation Factor Receptor
B-Lymphocytes / metabolism
B-Lymphocytes / physiology*
Cell Line
Cell Membrane / metabolism
DNA, Complementary / metabolism
Dose-Response Relationship, Drug
Flow Cytometry
Gene Library
Humans
Kinetics
Ligands
Membrane Proteins*
Neuropeptides / physiology*
Nuclear Proteins / physiology*
Polymerase Chain Reaction
Protein Binding
RNA, Messenger / metabolism
Receptors, Tumor Necrosis Factor / metabolism
Receptors, Tumor Necrosis Factor / physiology*
Recombinant Fusion Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Time Factors
Transfection
Transmembrane Activator and CAML Interactor Protein
Tumor Necrosis Factor-alpha / chemistry*

Substances

ANP32B protein, human
B-Cell Activation Factor Receptor
BLyS receptor
DNA, Complementary
Ligands
Membrane Proteins
Neuropeptides
Nuclear Proteins
RNA, Messenger
Receptors, Tumor Necrosis Factor
Recombinant Fusion Proteins
TNFRSF13B protein, human
TNFRSF13C protein, human
Transmembrane Activator and CAML Interactor Protein
Tumor Necrosis Factor-alpha