RECONSTITUTION OF SYK FUNCTION BY THE ZAP-70 PROTEIN-TYROSINE KINASE
RECONSTITUTION OF SYK FUNCTION BY THE ZAP-70 PROTEIN-TYROSINE KINASE
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DOI：
10.1016/1074-7613(95)90029-2
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发表时间：
1995-05-01
期刊：
影响因子：
32.4
通讯作者：
CHAN, AC
中科院分区：
文献类型：
--
作者：
KONG, GH;BU, JY;CHAN, AC
ZAP-70和Syk分别是TCR和BCR功能所需的PTK。Syk PTK的缺失导致无功能的BCR。我们通过证明ZAP-70在Syk（-）B细胞中的表达重建BCR功能，提供了ZAP-70和Syk在抗原受体信号传导中功能同源的证据。重建需要存在功能性Src同源2（SH 2）和ZAP-70的催化结构域。因此，药物靶向ZAP-70内的单个SH 2结构域应足以抑制造血抗原受体功能。此外，我们证明ZAP-70和Syk都可以直接结合磷酸化的IG α和IG β亚基，其亲和力与它们结合TCR CD 3 β亚基的亲和力相当。这些数据表明，ZAP-70和Syk在介导造血抗原受体信号传导的能力方面是相当的。
ZAP-70 and Syk are PTKs required for TCR and BCR function, respectively. Loss of the Syk PTK results in a nonfunctional BCR. We provide evidence here that ZAP-70 and Syk are functionally homologous in antigen receptor signaling by demonstrating that expression of ZAP-70 in Syk(-) B cells reconstitutes BCR function. Reconstitution required the presence of functional Src homology 2 (SH2) and catalytic domains of ZAP-70. Thus, drug targeting of a single SH2 domain within ZAP-70 should be sufficient to inhibit hematopoietic antigen receptor function. In addition, we demonstrate that both ZAP-70 and Syk can bind directly to the phosphorylated Ig alpha and Ig beta subunits with affinities comparable to their binding to the TCR CD3 epsilon subunit. These data suggest that ZAP-70 and Syk are comparable in their abilities to mediate hematopoietic antigen receptor signaling.