Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development.
The nature of signals that govern the development of immunoglobulin heavy chain-dependent B cells is largely unknown. Using mice deficient for the B cell-expressed Src-family protein tyrosine kinases (SFKs) Blk, Fyn and Lyn, we show an essential role of these kinases in pre-B cell receptor (pre-BCR)- mediated NF-kappaB activation and B cell development. This signaling defect is SFK specific, as a deficiency in Syk, which controls pre-B cell development, does not affect NF-kappaB induction. Impaired NF-kappaB induction was overcome by the activation of protein kinase C (PKC)-lambda, thus suggesting the involvement of PKC-lambda in pre-BCR-mediated SFK-dependent activation of NF-kappaB. Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development.
Saijo
Kaoru
K
Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021, USA. saijok@mail.rockefeller.edu
Schmedt
Christian
C
Su
I-Hsin
IH
Karasuyama
Hajime
H
Lowell
Clifford A
CA
Reth
Michael
M
Adachi
Takahiro
T
Patke
Alina
A
Santana
Angela
A
Tarakhovsky
Alexander
A
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016328:NF-kappa B; D019061:src-Family Kinases