Abstract
In recent years, the lymphocyte-specific protein tyrosine kinase (Lck) has emerged as one of the key molecules regulating T-cell functions. Studies using Lck knock-out mice or Lck-deficient T-cell lines have shown that Lck regulates the initiation of TCR signaling, T-cell development, and T-cell homeostasis. Because of the crucial role of Lck in T-cell responses, strategies have been employed to redirect Lck activity to improve the efficacy of chimeric antigen receptors (CARs) and to potentiate T-cell responses in cancer immunotherapy. In addition to the well-studied role of Lck in T cells, evidence has been accumulated suggesting that Lck is also expressed in the brain and in tumor cells, where it actively takes part in signaling processes regulating cellular functions like proliferation, survival and memory. Therefore, Lck has emerged as a novel druggable target molecule for the treatment of cancer and neuronal diseases. In this review, we will focus on these new functions of Lck.
Highlights
The lymphocyte-specific protein tyrosine kinase (Lck) is a member of the Src family of protein tyrosine kinases firstly identified in the 1980s [1,2]
Lck remains in many ways an enigmatic protein and recent research has provided new insights into the function of Lck in T-cell activation mediated by chimeric antigen receptors (CARs), in signal transmission in cancer cells, and in the brain
An alternative model postulates that a pool of activated Lck, which is present in resting T cells and constitutes about 40% of total Lck, is sufficient for T-cell activation and that the levels of Lck phosphorylated on Y394 do not change upon TCR stimulation [18]
Summary
The lymphocyte-specific protein tyrosine kinase (Lck) is a member of the Src family of protein tyrosine kinases firstly identified in the 1980s [1,2]. The function of Lck has been extensively investigated and many mechanistic insights into the regulation of its activity have been revealed. Lck remains in many ways an enigmatic protein and recent research has provided new insights into the function of Lck in T-cell activation mediated by chimeric antigen receptors (CARs), in signal transmission in cancer cells, and in the brain. We summarize recent advances on Lck biology in TCR signaling and on its role in the new emerging research fields
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