Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Health Campus Immunology, Infectiology and Inflammation (GC-I3), Medical Faculty, Otto-von Guericke University, 39120 Magdeburg, Germany.
Int J Mol Sci. 2020 Dec 24;22(1):126. doi: 10.3390/ijms22010126.
Lymphocyte-specific protein tyrosine kinase (Lck) is a pivotal tyrosine kinase involved in T cell receptor (TCR) signaling. Because of its importance, the activity of Lck is regulated at different levels including phosphorylation of tyrosine residues, protein-protein interactions, and localization. It has been proposed that the co-chaperone Cdc37, which assists the chaperone heat shock protein 90 (Hsp90) in the folding of client proteins, is also involved in the regulation of the activity/stability of Lck. Nevertheless, the available experimental data do not clearly support this conclusion. Thus, we assessed whether or not Cdc37 regulates Lck. We performed experiments in which the expression of Cdc37 was either augmented or suppressed in Jurkat T cells. The results of our experiments indicated that neither the overexpression nor the suppression of Cdc37 affected Lck stability and activity. Moreover, TCR signaling proceeded normally in T cells in which Cdc37 expression was either augmented or suppressed. Finally, we demonstrated that also under stress conditions Cdc37 was dispensable for the regulation of Lck activity/stability. In conclusion, our data do not support the idea that Lck is a Cdc37 client.
淋巴细胞特异性蛋白酪氨酸激酶（Lck）是一种在 T 细胞受体（TCR）信号转导中起关键作用的酪氨酸激酶。由于其重要性，Lck 的活性受到包括酪氨酸残基磷酸化、蛋白质-蛋白质相互作用和定位在内的不同水平的调节。有人提出，共伴侣 Cdc37 参与 Lck 活性/稳定性的调节，它协助伴侣热休克蛋白 90（Hsp90）折叠客户蛋白。然而，现有的实验数据并不清楚地支持这一结论。因此，我们评估了 Cdc37 是否调节 Lck。我们在 Jurkat T 细胞中分别过表达或敲低 Cdc37 的表达，进行了实验。我们的实验结果表明，Cdc37 的过表达或敲低既不影响 Lck 的稳定性，也不影响其活性。此外，TCR 信号转导在 Cdc37 过表达或敲低的 T 细胞中正常进行。最后，我们证明在应激条件下，Cdc37 对于 Lck 活性/稳定性的调节也是可有可无的。总之，我们的数据不支持 Lck 是 Cdc37 客户蛋白的观点。
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