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首页> 外文期刊>Molecular and Cellular Biology >Differential T-Cell Antigen Receptor Signaling Mediated by the Src Family Kinases Lck and Fyn
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Differential T-Cell Antigen Receptor Signaling Mediated by the Src Family Kinases Lck and Fyn

机译：Src家族激酶Lck和Fyn介导的差异性T细胞抗原受体信号传导。

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Src family tyrosine kinases play a key role in T-cell antigen receptor (TCR) signaling. They are responsible for the initial tyrosine phosphorylation of the receptor, leading to the recruitment of the ZAP-70 tyrosine kinase, as well as the subsequent phosphorylation and activation of ZAP-70. Molecular and genetic evidence indicates that both the Fyn and Lck members of the Src family can participate in TCR signal transduction; however, it is unclear to what extent they utilize the same signal transduction pathways and activate the same downstream events. We have addressed this issue by examining the ability of Fyn to mediate TCR signal transduction in an Lck-deficient T-cell line (JCaM1). Fyn was able to induce tyrosine phosphorylation of the TCR and recruitment of the ZAP-70 kinase, but the pattern of TCR phosphorylation was altered and activation of ZAP-70 was defective. Despite this, the SLP-76 adapter protein was inducibly tyrosine phosphorylated, and both the Ras–mitogen-activated protein kinase and the phosphatidylinositol 4,5-biphosphate signaling pathways were activated. TCR stimulation of JCaM1/Fyn cells induced the expression of the CD69 activation marker and inhibited cell growth, but NFAT activation and the production of interleukin-2 were markedly reduced. These results indicate that Fyn mediates an alternative form of TCR signaling which is independent of ZAP-70 activation and generates a distinct cellular phenotype. Furthermore, these findings imply that the outcome of TCR signal transduction may be determined by which Src family kinase is used to initiate signaling.
机译：Src家族的酪氨酸激酶在T细胞抗原受体（TCR）信号传导中起关键作用。它们负责受体的最初酪氨酸磷酸化，导致ZAP-70酪氨酸激酶的募集，以及随后的ZAP-70磷酸化和激活。分子和遗传学证据表明，Src家族的Fyn和Lck成员均可参与TCR信号转导。然而，尚不清楚它们在多大程度上利用了相同的信号转导途径并激活了相同的下游事件。我们已经通过检查Fyn在Lck缺陷型T细胞系（JCaM1）中介导TCR信号转导的能力来解决此问题。 Fyn能够诱导TCR的酪氨酸磷酸化和ZAP-70激酶的募集，但是TCR磷酸化的模式发生了改变，ZAP-70的激活存在缺陷。尽管如此，SLP-76衔接蛋白还是被酪氨酸磷酸化，并且Ras-丝裂原活化的蛋白激酶和磷脂酰肌醇4,5-二磷酸信号通路均被激活。 TCR刺激JCaM1 / Fyn细胞诱导CD69激活标志物的表达并抑制细胞生长，但NFAT激活和白介素2的产生明显减少。这些结果表明，Fyn介导了另一种形式的TCR信号传导，该信号传导独立于ZAP-70激活并产生独特的细胞表型。此外，这些发现暗示TCR信号转导的结果可以通过使用哪种Src家族激酶来启动信号来确定。

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