Expression and function of B cell specific MB-1 protein associated with IgM receptor

与 IgM 受体相关的 B 细胞特异性 MB-1 蛋白的表达和功能

• 批准号: 05454209
• 负责人: SAKAGUCHI Nobuo
• 金额: $ 4.67万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454209/
• 关键词: B cell; Antigen receptor; MB-1; signal transduction; Apoptosis; トレランス; MB-1

B cell antigent receptor is composed of antigen specific membrane IgM molecule and its associated proteins of MB-1 (Ig-alpha, CD79a) and B29 (Ig-beta, CD79b) .This basic structure is essential not only for the expression of B cell antigen receptor on the surface of B lymphocytes but also for signal transduction of stimulatory signal given by antigen. Within cytoplasmic domains of MB-1 and B29, there are antigen recognition consensus motif that can bind to various functional components related to the signal transduction. B cell antigen receptor complex involves src-type tyrosine kinase Lyn, Fyn, Lck, Blk, non src-tyupe tyrosine kinase Syk, and PI-3 kinase. Crosslinking of antigen receptor induces signal transduction of phosphatidyl inositol patyways, leading to the increase of intracellular Ca mobilization and protein kinase sctivity. It also induces signal transduction of ras-MECK/MAPK pathway leading to activation of nuclear transcription factors. Activation to antigen receptor on B cells also induces PI-3 kinase activity which then probably mediates important signal for the proliferation and differentiation of B cells.Regardless of these fundamental findings concerning to B cell signal transduction pathways, little is known about the mechanism and quality of signal transduction through these signal transduction pathways in different stages of B lineage cells. To clearly identify novel molecules involved in the B cell antigen receptor complex, we searched for the functional phosphoprotein molecules associated with MB-1 protein. A 52 kDa protein is coprecipitated with anti-MB-1 protein. We prepared rat monoclonal antibody against this 52 kDa protein and isolated a candidate cDNA clone named alpha4 with this monoclonal antibody. The alpha4 cDNA clone is a new molecule which is tightly associated with kinase molecules in B cells, which is located in the down stream of the signal transduction through B cell antigen raceptor.

B细胞抗原受体由抗原特异性膜IgM分子及其相关蛋白MB-1 （ig - α, CD79a）和B29 （ig - β, CD79b）组成。这一基本结构不仅对B淋巴细胞表面B细胞抗原受体的表达至关重要，而且对抗原给予的刺激信号的信号转导也至关重要。在MB-1和B29的细胞质结构域内，存在抗原识别共识基序，可以结合与信号转导相关的各种功能成分。B细胞抗原受体复合物包括src型酪氨酸激酶Lyn、Fyn、Lck、Blk、非src型酪氨酸激酶Syk和PI-3激酶。抗原受体的交联诱导磷脂酰肌醇途径的信号转导，导致细胞内Ca动员和蛋白激酶活性的增加。它还可以诱导ras-MECK/MAPK通路的信号转导，从而激活核转录因子。B细胞抗原受体的活化还可诱导PI-3激酶活性，从而可能介导B细胞增殖和分化的重要信号。尽管有这些关于B细胞信号转导途径的基本发现，但对B系细胞不同阶段通过这些信号转导途径进行信号转导的机制和质量知之甚少。为了清楚地识别参与B细胞抗原受体复合物的新分子，我们寻找了与MB-1蛋白相关的功能性磷酸化蛋白分子。52kda蛋白与抗mb -1蛋白共沉淀。我们制备了抗该52 kDa蛋白的大鼠单克隆抗体，并分离了一个候选cDNA克隆，命名为alpha4。alpha4 cDNA克隆是B细胞中与激酶分子紧密相关的新分子，位于B细胞抗原受体信号转导的下游。

项目成果

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Kuwahara,K.: "Identification of a 52-kDa molecule(p52)co-precipitated with the immunoglobulin receptor-related MB-1 protein which is inducibly phosphorylated by the stimulation with phorbol myristate acetate" J.Immunol.(印刷中).

Kuwahara, K.：“鉴定与免疫球蛋白受体相关的 MB-1 蛋白共沉淀的 52 kDa 分子 (p52)，该蛋白通过佛波醇肉豆蔻酸酯乙酸酯的刺激而诱导磷酸化”J.Immunol。

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