| Budget Amount *help |
¥49,140,000 (Direct Cost: ¥37,800,000、Indirect Cost: ¥11,340,000)
Fiscal Year 2007: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2006: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
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| Research Abstract |
In terms of BCR signaling, we focused our research on a family of adaptor molecules : BLNK, BCAP, BANK and CAR1VIAL We elucidated the mechanisms for these molecules when coupled with various receptor, adaptor and effector families. Specifically, we determined the following three results.
1. CARMA1 is phosphorylated by PKC (3 and IKK. CARMA1 is required for NF-KB activation. During the project, we determined several phosphorylation sites on CARMA1, specifically: 1) Ser668 is phosphorylated by PKC (3 and is critical to the initial activation of IKK, and 2) subsequently Ser557 is phosphorylated.
2. BCAP, together with CD19, plays an essential role in recruiting and activating PI3 kinase (PI3K) at the cell membrane. An adaptor molecule BCAP, as well as CD19, binds PI3K. One possible idea is that BCAP plays an essential role in PI3K activation together with CD19. To examine this possibility directly, we made CD19/BCAP double-knockout mice. B cells from these mice virtually lack PI3K activation, resulting in the arrest of B lymphocyte development at the pre-BCR stage. These results strongly support our hypothesis.
3. BLNK is essential for SOC channel activation It is considered that upon BCR stimulation, calcium is released from the intracellular pool into the cytoplasm, which triggers the opening of SOC channels in the cell membrane. BLNK is known to play a vital role in PLCγ2 activation. During this research project we determined that BLNK also contributes to the formation of channelsomes and plays an important role in opening SOC channels.
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