TY - JOUR
T1 - Deficiency of BLNK hampers PLC-γ2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells
AU - Taguchi, Tomoko
AU - Kiyokawa, Nobutaka
AU - Takenouch, Hisami
AU - Matsui, Jun
AU - Tang, Wei Ran
AU - Nakajima, Hideki
AU - Suzuki, Kyoko
AU - Shiozawa, Yusuke
AU - Saito, Masahiro
AU - Katagiri, Yohko U.
AU - Takahashi, Takao
AU - Karasuyama, Hajime
AU - Matsuo, Yoshinobu
AU - Okita, Hajime
AU - Fujimoto, Junichiro
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/8
Y1 - 2004/8
N2 - B-cell linker protein (BLNK) is a component of the B-cell receptor (BCR) as well as of the pre-BCR signalling pathway, and BLINK-/- mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. A recent report described the complete loss or drastic reduction of BLNK expression in approximately 50% of human childhood pre-B acute lymphoblastic leukaemias (ALL), therefore we investigated BLNK expression in human pre-B ALL cell lines. One of the four cell lines tested, HPB-NULL cells, was found to lack BLNK expression, and we used these human pre-B ALL cell lines that express and do not express BLNK to investigate the intracellular signalling events following pre-BCR cross-linking. When pre-BCR was cross-linked with anti-μ heavy-chain antibodies, significant phosphorylation of intracellular molecules, including Syk, Shc, ERK MAP kinase, and AKT, and an activation of Ras were observed without regard to deficiency of BLNK expression, suggesting that BLNK is not required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signalling. By contrast, phospholipase C-γ2 (PLC-γ2) phosphorylation and an increase in intracellular Ca2+ level mediated by pre-BCR cross-linking were observed only in the BLNK-expressing cells, indicating that BLNK is essential for PLC-γ2-induced Ca2+ influx. Human pre-B cell lines expressing and not expressing BLNK should provide an in vitro model for investigation of the role of BLNK in the pre-BCR-mediated signalling mechanism.
AB - B-cell linker protein (BLNK) is a component of the B-cell receptor (BCR) as well as of the pre-BCR signalling pathway, and BLINK-/- mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. A recent report described the complete loss or drastic reduction of BLNK expression in approximately 50% of human childhood pre-B acute lymphoblastic leukaemias (ALL), therefore we investigated BLNK expression in human pre-B ALL cell lines. One of the four cell lines tested, HPB-NULL cells, was found to lack BLNK expression, and we used these human pre-B ALL cell lines that express and do not express BLNK to investigate the intracellular signalling events following pre-BCR cross-linking. When pre-BCR was cross-linked with anti-μ heavy-chain antibodies, significant phosphorylation of intracellular molecules, including Syk, Shc, ERK MAP kinase, and AKT, and an activation of Ras were observed without regard to deficiency of BLNK expression, suggesting that BLNK is not required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signalling. By contrast, phospholipase C-γ2 (PLC-γ2) phosphorylation and an increase in intracellular Ca2+ level mediated by pre-BCR cross-linking were observed only in the BLNK-expressing cells, indicating that BLNK is essential for PLC-γ2-induced Ca2+ influx. Human pre-B cell lines expressing and not expressing BLNK should provide an in vitro model for investigation of the role of BLNK in the pre-BCR-mediated signalling mechanism.
KW - B cells
KW - B-cell receptor
KW - Signalling/signal transduction
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U2 - 10.1111/j.1365-2567.2004.01918.x
DO - 10.1111/j.1365-2567.2004.01918.x
M3 - Article
C2 - 15270728
AN - SCOPUS:4043075523
SN - 0019-2805
VL - 112
SP - 575
EP - 582
JO - Immunology
JF - Immunology
IS - 4
ER -