P56(LCK)-INDEPENDENT ACTIVATION AND TYROSINE PHOSPHORYLATION OF P72(SYK) BY T-CELL ANTIGEN RECEPTOR/CD3 STIMULATION
P56(LCK)-INDEPENDENT ACTIVATION AND TYROSINE PHOSPHORYLATION OF P72(SYK) BY T-CELL ANTIGEN RECEPTOR/CD3 STIMULATION
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DOI：
10.1073/pnas.91.12.5301
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
MUSTELIN, T
中科院分区：
文献类型：
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作者：
COUTURE, C;BAIER, G;MUSTELIN, T
T细胞抗原受体(TCR)/CD3复合物的配体激活静止T淋巴细胞是由细胞蛋白的快速酪氨酸磷酸化启动的。src家族的蛋白酪氨酸激酶（PTKs）已知是重要的，但它们的募集机制及其与其他家族PTKs的相互作用尚不完全清楚。我们发现另一个PTKs家族的成员p72（syk）激酶组成性地结合到TCR/CD3复合物上，并在TCR/CD3刺激后1分钟内被酪氨酸磷酸化并激活。这种激活不依赖于T细胞和转染的COS细胞中p56（lck）的存在。然而，在这两种情况下，细胞底物的磷酸化都被src家族PTKs增强了。我们提出p72（syk）可能在T细胞中作为相关p70(zap) PTK和src家族PTK p56（lck）和p59（fyn）上游的直接受体激活激酶，这些src家族PTK作为信号放大器。
Activation of resting T lymphocytes by ligands to the T-cell antigen receptor (TCR)/CD3 complex is initiated by rapid tyrosine phosphorylation of cellular proteins. Protein-tyrosine kinases (PTKs) of the src family are known to be important, but the mechanism of their recruitment and their interactions with PTKs of other families are incompletely understood. We show that a member of another family of PTKs, the p72(syk) kinase, is constitutively bound to the TCR/CD3 complex and becomes tyrosine phosphorylated and activated within 1 min after TCR/CD3 stimulation. This activation did not depend on the presence of p56(lck) in T cells and in transfected COS cells. In both cases, however, the phosphorylation of cellular substrates was augmented by src family PTKs. We propose that p72(syk) may act as an immediate receptor-activated kinase upstream of the related p70(zap) PTK and the src family PTKs p56(lck) and p59(fyn) in T cells and that these src family PTKs act as signal amplifiers.