Functional analysis of Lyn kinase A and B isoforms reveals redundant and distinct roles in Fc epsilon RI-dependent mast cell activation.
Functional analysis of Lyn kinase A and B isoforms reveals redundant and distinct roles in Fc epsilon RI-dependent mast cell activation.
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DOI：
10.4049/jimmunol.0904064
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发表时间：
2010-05-01
期刊：
影响因子：
--
通讯作者：
Rivera J
中科院分区：
文献类型：
--
作者：
Alvarez-Errico D;Yamashita Y;Suzuki R;Odom S;Furumoto Y;Yamashita T;Rivera J
免疫球蛋白E高亲和力受体(Fc、ε、RI)的结合导致其被Lyn激酶磷酸化。两个选择性剪接变异体Lyn A和B在肥大细胞中表达，这两种异构体都与FcεRI相互作用。与LYN A不同，LYN B在NH2末端的唯一结构域中缺少21个氨基酸区域。在这里，我们研究了Lyn A和B亚型在肥大细胞信号和反应中的作用。研究发现，Lyn B不是肥大细胞脱颗粒的诱导剂，在产生IP3和钙反应方面也不太有效。LYN B单独表达显示磷脂酶Cγ-1和2的磷酸化程度降低，磷脂酶Cγ-1与激活T细胞的磷酸化连接物的相互作用减少。Lyn B还显示酪氨酸磷酸化蛋白的结合增加，其中包括负调控的脂质磷酸酶SHIP-1。相反，LYN A和LYN B都引起相似的细胞总酪氨酸磷酸化和FcεRI磷酸化，并且LYN A和LYN B都不能完全恢复肥大细胞脱颗粒或抑制在没有LYN的情况下过度产生的细胞因子。然而，这两种异构体的表达表现出互补和标准化反应。这些发现表明，LYN B与LYN A在与SHIP-1的结合和钙反应的调节方面不同。然而，肥大细胞的激活需要两种亚型的互补。
Engagement of the high affinity receptor for IgE (FcεRI) causes its phosphorylation by Lyn kinase. Two alternatively spliced variants, Lyn A and B are expressed in mast cells and both isoforms interact with FcεRI. Unlike Lyn A, Lyn B lacks a 21 amino acid region in the NH2-terminal unique domain. Here we investigated the role of Lyn A and B isoforms in mast cell signaling and responses. Lyn B was found to be a poor inducer of mast cell degranulation and was less potent in both IP3 production and calcium responses. Expression of Lyn B alone showed reduced phosphorylation of both phospholipase Cγ-1 and 2 and decreased interaction of phospholipase Cγ-1 with the phosphorylated linker for activation of T cells. Lyn B also showed increased binding of tyrosine phosphorylated proteins, which included the negative regulatory lipid phosphatase SHIP-1. In contrast, both Lyn A and B caused similar total cellular tyrosine phosphorylation and FcεRI phosphorylation and neither Lyn A nor Lyn B alone could completely restore mast cell degranulation or dampen the excessive cytokine production seen in the absence of Lyn. However, expression of both isoforms showed complementation and normalized responses. These findings demonstrate that Lyn B differs from Lyn A in its association with SHIP-1 and in the regulation of calcium responses. However, complementation of both isoforms is required in mast cell activation.
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影响因子：
4.8
作者：
Liang, XQ;Wisniewski, D;Resh, MD
通讯作者：
Resh, MD
影响因子：
64.8
作者：
Prakriya, Murali;Feske, Stefan;Hogan, Patrick G.
通讯作者：
Hogan, Patrick G.
DOI：
10.1073/pnas.92.20.9201
发表时间：
1995-09-26
影响因子：
11.1
作者：
FIELD, KA;HOLOWKA, D;BAIRD, B
通讯作者：
BAIRD, B
影响因子：
15.3
作者：
Hata, D;Kawakami, Y;Inagaki, N;Lantz, CS;Kitamura, T;Khan, WN;Maeda-Yamamoto, M;Miura, T;Han, W;Hartman, SE;Yao, L;Nagai, H;Goldfeld, AE;Alt, FW;Galli, SJ;Witte, ON;Kawakami, T
通讯作者：
Kawakami, T
影响因子：
32.4
作者：
Olivera, Ana;Mizugishi, Kiyomi;Rivera, Juan
通讯作者：
Rivera, Juan