In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets.
[6] 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.
Lck can be found in different forms in 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, Lck is able to bind the cell surface coreceptors CD8 and\or CD4.
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.
The T cells maturation occurs in the thymus and it is regulated by a threshold that defines the limit between the positive and the negative selection of thymocytes.
The phosphorylated form of ZAP-70 recruits another molecule in the signaling cascade called LAT (Linker for activation of T cells), a transmembrane protein.
Mice express low levels of high molecular weight isoforms (CD45RABC) in thymocytes or peripheral T cells.
[18] In general, CD45 acts to promote the active form of LCK by dephosphorylating a tyrosine (Y192) in its inhibitory C-terminal tail.
[7] In contrast, Csk has an opposite role to that of CD45, it phosphorylated the Y505 of Lck promoting the closed conformation with inhibited kinase activity.
Many pathologies are linked to the overexpression of Lck such as cancer, asthma, diabetes 1, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, inflammatory bowel diseases (Crohn's disease and ulcerative colitis), organ graft rejection, atherosclerosis, hypersensitivity reactions, polyarthritis, dermatomyositis.
Tumorigenesis is enhanced by abnormal proliferation of immature thymocytes due to low levels of Lck.
[21] Moreover, mice with an unbalanced amount of lck show altered lung function which can consequentially leads to the onset of asthma.
[25] HSP90 inhibitor NVP-BEP800 has been described to affect stability of the LCK kinase and growth of T-cell acute lymphoblastic leukemias.