GPI-anchored protein-mediated cell signaling system in B-precursor cells
| Project/Area Number |
15590361
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
KIYOKAWA Nobutaka National Research Institute for Child Health and Development, Dpt. of Developmental Biology, Director, 発生・分化研究部, 部長 (60195401)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | B-precursor cells / GPI-anchored / cell signaling system / Lipids rafts / Differentiation / Pre-B cell antigen receptor / Bone marrow stromal cells / 糖脂質豊富膜ドメイン / BLNK |
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| Research Abstract |
We previously reported that the cross-linking of cluster of differentiation (CD)24 induces apoptosis in Burkitt's lymphoma cells as well as B-predursor ALL cells. CD24 is a GPI-anchored protein and this apoptosis induction is mediated by raft microdomain-mediated cell signaling system. To investigate the cell signaling mediated by GPI-anchored protein in normal B precursor cells, we developed an in vitro culture system to differentiate CD34+ cells into pro-B cells. Using this culture system, we found that the cross-linking of CD24 induced apoptosis in normal human pro-B cells.
B-cell linker protein (BLNK) is a component of the B-cell receptor (BCR) signalling pathway, in which raft microdomain is deeply involved. We investigated BLNK expression in human pre-B ALL cell lines and found that 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-gamma2 (PLC-gamma2) phosphorylation and an increase in intracellular Ca(2+) level mediated by pre-BCR cross-linking were observed only in the BLNK-expressing cells, indicating that BLNK is essential for PLC-gamma2-induced Ca(2+) influx.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Deficiency of BLNK hampers PLC-γ2 phosphorylation and Ca^<2+> influx induced by the pre- cell receptor in human pre-B cells.2004
Author(s)
Taguchi T, Kiyokawa N, Takenouchi H, Matsui J, Tang W, Nakajima H, Suzuki K, Shiozawa Y, Saito M, Katagiri YU, Takahshi T, Karasuyama H, Matsuo Y, Okita H, Fujimoto J.
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Journal Title
Immunology 112
Pages: 575-582
Related Report
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[Journal Article] Diagnostic importance of CD179a/b as markers of precursor B-cell lymphoblastic lymphoma.2004
Author(s)
Kiyokawa N, Sekino T, Matsui T, Takenouchi H, Mimori K, Tang W, Matsui J, Taguchi T, Katagiri YU, Okita H, Matsuo Y, Karasuyama H, Fujimoto J.
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Journal Title
Modern Pathol 17
Pages: 423-429
Related Report
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[Journal Article] Dietary bioflavonoids induce apoptosis in human leukemia cells.
Author(s)
Matsui J, Kiyokawa N, Takenouchi H, Taguchi T, Suzuki K, Shiozawa Y, Saito M, Tang W-R, Katagiri YU, Okita H, Fujimoto J.
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Journal Title
Leukemia Research (in press)
Related Report
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