Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS.
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.
Wu
Y
Y
Department of Molecular Biology, Human Genome Sciences, Inc., Rockville, Maryland 20850, USA.
Bressette
D
D
Carrell
J A
JA
Kaufman
T
T
Feng
P
P
Taylor
K
K
Gan
Y
Y
Cho
Y H
YH
Garcia
A D
AD
Gollatz
E
E
Dimke
D
D
LaFleur
D
D
Migone
T S
TS
Nardelli
B
B
Wei
P
P
Ruben
S M
SM
Ullrich
S J
SJ
Olsen
H S
HS
Kanakaraj
P
P
Moore
P A
PA
Baker
K P
KP
D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008565:Membrane Proteins; D009479:Neuropeptides / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
C490341:ANP32B protein, human; D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D018076:DNA, Complementary; D008024:Ligands; D008565:Membrane Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha