Diminished tyrosine protein kinase activity in T cells unresponsive to TCR stimulation.
Diminished tyrosine protein kinase activity in T cells unresponsive to TCR stimulation.
复制标题
对 TCR 刺激无反应的 T 细胞中酪氨酸蛋白激酶活性降低。
DOI：
10.1002/jlb.55.3.289
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发表时间：
1994
影响因子：
5.5
通讯作者：
Bolen,JB
中科院分区：
文献类型：
--
作者：
Tsygankov,AY;Kim,HW;Pratt,JC;Spana,C;Class,K;Gaulton,GN;Kamoun,M;Bolen,JB
酪氨酸磷酸化被认为是T细胞抗原活化的最早步骤之一。已知三种非受体酪氨酸激酶p56 lck、p60 fyn和ZAP-70参与T细胞受体（TCR）信号传导，尽管它们的功能作用似乎不同。尽管p60 fyn和ZAP-70在功能上与T细胞抗原受体相关，但p56 lck对于TCR信号传导是必需的，而不直接与TCR偶联。我们已经研究了Jurkat T细胞系（J32-3.2）的突变变体，其中p56 lck和p60 fyn的基础活性相对于其亲本系（J32）中的那些降低2至2.5倍，而ZAP-70的基础活性保持不变，并且比较了J32-3.2和J32对TCR刺激的反应。我们已经证明，在J32-3.2细胞中CD 3交联后的酪氨酸磷酸化是非常短暂的，因此不足以诱导随后的生理反应。这至少部分是由于这些细胞中酪氨酸激酶活性的降低。src相关激酶活性的降低主要是由于它们的低表达引起的，而ZAP-70的表达没有变化，但其对CD 3交联的反应减弱，这与最近在J32-3.2中观察到的CD 3链的酪氨酸磷酸化缺陷有关。这些数据与sir相关激酶磷酸化β-链的想法一致，β-链进而募集维持信号所需的ZAP-70。55：289-298; 1994.
Tyrosine phosphorylation is thought to be one of the earliest steps in antigenic activation of T cells. Three nonreceptor tyrosine kinases,p56lck, p60fyn,and ZAP-70, are known to be involved in T cell receptor (TCR) signaling, albeit their functional roles appear to be different. Whereas p60fynand ZAP-70 are functionally associated with the T cell antigen receptor, p56lckis essential for TCR signaling without being directly coupled to the TCR. We have studied a mutant variant of the Jurkat T cell line (J32–3.2), in which basal activities of p56lckand p60fynare 2- to 2.5-fold reduced relative to those in its parental line (J32) while basal activity of ZAP-70 remains unchanged, and compared responses of J32–3.2 and J32 to TCR stimulation. We have demonstrated that tyrosine phosphorylation following CD3 cross-linking in J32–3.2 cells was extremely short-lived and thus insufficient for the induction of subsequent physiological responses. This was at least partially due to the diminished tyrosine kinase activity in these cells. A decrease in the activity ofsrc-related kinases was caused primarily by their lower expression, whereas expression of ZAP-70 was unchanged but its response to CD3 crosslinking was diminished, correlating with the deficient tyrosine phosphorylation of the CD3 -chain, recently observed in J32–3.2. These data are consistent with the idea that sir-related kinases phosphorylate the -chain, which in turn recruits ZAP-70 required to sustain the signal.J. Leukoc. Biol.55: 289–298; 1994.