Yamamoto T, Yamanashi Y, Takeuchi M, Fusaki N, Uchiumi F, Katagiri T, Semba K, Toyoshima K
Institute of Medical Science, University of Tokyo, Japan.
Princess Takamatsu Symp. 1991;22:293-305.
Cross-linking of membrane-bound immunoglobulins, which are B cell antigen receptors, causes proliferation and differentiation of B cells or the inhibition of their growth. The receptor-mediated signalling involves tyrosine phosphorylation of cellular proteins. The Src-like protein-tyrosine kinase Lyn is expressed preferentially in B cells and is an intracytoplasmic constituent of the B cell antigen receptor complex. Cross-linking of membrane-bound immunoglobulin M with antibody induced rapid increases in the kinase activities of Lyn and Lyn-associated phosphatidylinositol-3 kinase. Cross-linking of B-cell antigen receptor also induced association of Lyn with an 85 kDa non-catalytic subunit of phosphatidylinositol-3 kinase. Thus, Lyn is functionally associated with membrane-bound immunoglobulin M, and seems to participate in B cell antigen receptor-mediated signalling. On the other hand, accumulating evidence shows that Fyn and Lck are involved in T-cell activation. Co-immunoprecipitation experiments showed that Fyn was physically associated with T cell antigen receptor-CD3 complex. Transient expression of actively mutated Fyn, having Phe-528 instead of Tyr-528, in Jurkat T cells stimulated the fos promoter and serum response element (SRE), suggesting that the Fyn kinase stimulates c-fos expression through SRE. An analogous set of experiments showed that introduction of the active Fyn alone had little effect on IL-2 promoter. However, it could stimulate transcription from this promoter when transfected cells were stimulated by a combination of Concanavalin A (ConA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). Under the same conditions, normal Lck and Lyn could not stimulate IL-2 promoter.
作为B细胞抗原受体的膜结合免疫球蛋白的交联会导致B细胞增殖和分化或抑制其生长。受体介导的信号传导涉及细胞蛋白的酪氨酸磷酸化。Src样蛋白酪氨酸激酶Lyn优先在B细胞中表达，是B细胞抗原受体复合物的胞质内成分。膜结合免疫球蛋白M与抗体的交联导致Lyn和Lyn相关磷脂酰肌醇-3激酶的激酶活性迅速增加。B细胞抗原受体的交联还诱导Lyn与磷脂酰肌醇-3激酶的85 kDa非催化亚基结合。因此，Lyn在功能上与膜结合免疫球蛋白M相关，似乎参与B细胞抗原受体介导的信号传导。另一方面，越来越多的证据表明Fyn和Lck参与T细胞活化。免疫共沉淀实验表明Fyn与T细胞抗原受体-CD3复合物存在物理关联。在Jurkat T细胞中瞬时表达具有Phe-528而非Tyr-528的活性突变型Fyn可刺激fos启动子和血清反应元件（SRE），这表明Fyn激酶通过SRE刺激c-fos表达。一组类似的实验表明单独引入活性Fyn对IL-2启动子几乎没有影响。然而，当转染细胞受到刀豆球蛋白A（ConA）和12-O-十四烷酰佛波醇-13-乙酸酯（TPA）的联合刺激时，它可以刺激该启动子的转录。在相同条件下，正常的Lck和Lyn不能刺激IL-2启动子。
