Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk
Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk
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DOI：
10.1016/j.bbrc.2007.09.100
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发表时间：
2007-12-07
影响因子：
3.1
通讯作者：
Kurosaki, Tomohiro
中科院分区：
文献类型：
--
作者：
Adachi, Takahiro;Wienands, Juergen;Kurosaki, Tomohiro
非受体型蛋白酪氨酸激酶（PTK）Syk对于通过B细胞抗原受体（BCR）的信号传导是必需的。在BCR交联后，Syk通过其串联的SH 2结构域被募集到构成BCR组分的酪氨酸磷酸化的Ig-α/Ig-β，然后被活化。位于两个SH 2结构域之间的结构域间A在不同种类的Syk之间以及Syk和ZAP-70之间是高度保守的。突变体Syk在结构域间A（Delta 140-159）中携带缺失，无论BCR连接如何，都变得磷酸化，并且在BCR交联后不诱导Ca 2+动员。此外，体外结合测定显示，缺失一部分结构域间A消除了其与磷酸化Ig-α/Ig-β的结合活性。这些结果表明，Syk的结构域间A是通过在BCR连接后与磷酸化的Ig-α/Ig-β结合来激活Syk和抑制静息状态下的自发激活所必需的。(C)2007爱思唯尔公司All rights reserved.
Non-receptor type protein tyrosine kinase (PTK) Syk is essential for the signaling via the B cell antigen receptor (BCR). Upon BCR crosslinking, Syk is recruited via its tandem SH2 domains to tyrosine-phosphorylated Ig-alpha/Ig-beta constituting components of BCR, and is then activated. The interdomain A lying between the two SH2 domains is highly conserved among different species of Syk and between Syk and ZAP-70. The mutant Syk carrying a deletion in the interdomain A (Delta 140-159) became phosphorylated regardless of BCR ligation and did not induce Ca2+ mobilization upon crosslinking of BCR. Furthermore, in vitro binding assay revealed that deletion of a part of the interdomain A abolished its binding activity to phosphorylated Ig-alpha/Ig-beta. These results indicate that the interdomain A of Syk is required for activation of Syk by binding to the phosphorylated Ig-alpha/Ig-beta upon BCR ligation and inhibition of spontaneous activation at the resting state. (C) 2007 Elsevier Inc. All rights reserved.