|
|
|
|
|
|
|
||
Original Article |
b Kinase and Nuclear Factor b in Response to B Cell Receptor Engagement
Khanwn{at}ctrvax.vanderbilt.edu
Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-
B, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-B. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IB kinase (IKK), which normally targets the NF-B inhibitor IB
for degradation. Taken together, these findings indicate that BTK couples IKK and NF-B to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid.
Key Words: X-linked immunodeficiency • X-linked agammaglobulinemia • antigen receptor signaling • transcription factor • Tec family tyrosine kinase
B kinase; NF-B, nuclear factor B; PKC, protein kinase C; xid, X-linked immunodeficiency; XLA, X-linked agammaglobulinemia. © 2000 The Rockefeller University Press
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
