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Concept
Lck
Summary
Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK), it is important for the activation of the T-cell receptor signaling in both naive T cells and effector T cells. The role of the Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the role of the lck varies among the memory T cells subsets. It seems that in mice, in the effector memory T cells (TEM) population, more than 50% of lck is present in a constitutively active conformation, whereas, only less than 20% of lck is present as active form of lck. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.
The Lck is responsible for the initiation of the TCR signaling cascade inside the cell by phosphorylating immunoreceptor tyrosine‐based activation motifs (ITAM) within the TCR-associated chains.
The Lck can be found in different forms in the immune cells: free in the cytosol or bound to the plasma membrane (PM) through myristoylation and palmitoylation. Due to the presence of the conserved CxxC motif (C20 and C23) in the zinc clasp structure, the Lck is able to bind the cell surface coreceptors CD8 and\or CD4.
Bound and free Lck have different properties: free Lck have more pronounced kinase activity in comparison to bounded Lck, moreover, the free form produces a higher T cell activation. The reasons of these differences are not well understood yet.
Lck is most commonly found in T cells. It associates with the cytoplasmic tails of the CD4 and CD8 co-receptors on T helper cells and cytotoxic T cells, respectively, to assist signaling from the T cell receptor (TCR) complex. T cells are able to respond to pathogen and cancer using T-cell receptor, nevertheless, they can also react to self-antigen causing the onset of autoimmune diseases.
Official source
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