TYROSINE KINASES LYN AND SYK REGULATE B-CELL RECEPTOR-COUPLED CA2+ MOBILIZATION THROUGH DISTINCT PATHWAYS
TYROSINE KINASES LYN AND SYK REGULATE B-CELL RECEPTOR-COUPLED CA2+ MOBILIZATION THROUGH DISTINCT PATHWAYS
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DOI：
10.1002/j.1460-2075.1994.tb06387.x
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发表时间：
1994-03-15
期刊：
影响因子：
11.4
通讯作者：
KUROSAKI, T
中科院分区：
文献类型：
--
作者：
TAKATA, M;SABE, H;KUROSAKI, T
通过其抗原受体（BCR）刺激B淋巴细胞会导致酪氨酸磷酸化在多种蛋白质上的迅速增加，并诱导磷脂酰肌醇的增加以及细胞质游离钙的动员。 BCR与两类酪氨酸激酶相关联：SRC-家庭激酶（Lyn，Fyn，Blk或LCK）和Syk激酶。为了剖析这两种类型的激酶在BCR信号传导中的功能作用，建立了LYN阴性和SYK阴性B细胞系。缺乏SYK的B细胞消除了磷脂酶C-Gamma2的酪氨酸磷酸化，从而导致肌醇1,4,5-三磷酸（IP3）的产生和受体刺激时的钙动员丧失。尽管IP3转换的正常动力学，但在Lyn缺陷型细胞上的BCR在Lyn缺陷型细胞上的交联导致了延迟和缓慢的CA2+动员。这些结果表明SYK介导了IP3的生成，而Lyn通过独立于IP3生成的过程调节CA2+动员。
Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Lyn, Fyn, Blk or Lck) and Syk kinase. To dissect the functional roles of these two types of kinase in BCR signaling, lyn-negative and syk-negative B cell lines were established. Syk-deficient B cells abolished the tyrosine phosphorylation of phospholipase C-gamma2, resulting in the loss of both inositol 1,4,5-trisphosphate (IP3) generation and calcium mobilization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed and slow Ca2+ mobilization, despite the normal kinetics of IP3 turnover. These results demonstrate that Syk mediates IP3 generation, whereas Lyn regulates Ca2+ mobilization through a process independent of IP3 generation.