LCK

LCK is the acronym for "Lymphocyte-specific protein tyrosine kinase". LCK is a 56-kilodalton-heavy kinase that phosphorylates tyrosine residues of certain proteins involved in intracellular signaling pathways of lymphocytes. LCK is a member of the Src family (compound acronym from cellular and sarcoma) of tyrosine kinases.

LCK is most abundant in T lymphocytes. It associates with the cytoplasmic portions of CD4 and CD8 coreceptors on T helper cells and cytotoxic T cells, respectively, to support signal transduction by the T cell receptor complex (TCR).

When the T cell receptor is activated by a specific antigen presented by the MHC, the LCK protein phosphorylates the intracellular chains of CD3 and CD3-zeta (ζ-chains) of the TCR complex. Subsequently, another cytoplasmic tyrosine kinase, ZAP70, can bind to these chains. LCK phosphorylates and thereby activates ZAP70. ZAP70 in turn phosphorylates another molecule in the signaling cascade called LAT (LAT is the acronym for "linker for T cell activation"). LAT is a transmembrane protein that serves as a docking site for a number of other proteins.

The tyrosine phosphorylation cascade initiated by LCK and FYN leads to intracellular mobilization of calcium (Ca2+) ions and activation of key signaling cascades within the lymphocyte. This includes the Ras-MEK-ERK pathway.

The N-terminal tail of LCK is myristoylated and palmitoylated, which binds the protein to the plasma membrane of the cell. Lck phosphorylates a number of proteins, the most important of which are the CD3 receptor, CEACAM1, ZAP70, SLP-76, the IL-2 receptor, protein kinase C, ITK, PLC, SHC, RasGAP, Cbl, Vav1, and PI3K.