Lck, Active

Lck (p56lck) is a member of the src family of non-receptor tyrosine kinases. It was identified as a gene rearranged and overexpressed in the murine lymphoma LSTRA, most likely as a result of the insertion of Moloney murine leukemia virus DNA immediately adjacent to the gene. Lck behaves as a proto-oncogene and can lead to cell transformation upon activation. A number of human cancer cell lines show overexpression of Lck, pointing to a possible role for this kinase in the initiation and maintenance of the transformed state in human cancers. Colon cancers and T-cell leukemias frequently show defective regulation of Lck expression and activity.Inappropriate T cell activation and proliferation have been identified as an early event in auto-immune disease. Lck plays a prominent role in T-cell development, activation, proliferation and survival. Lck is coupled to both the CD4 and CD8 antigens (which serve as receptors for nonpolymorphic regions of products of the major histocompatibility complex and have been implicated in the regulation of T-cell growth) in T-cells and phosphorylates CD3. Lck phosphorylates many cellular protein substrates as a result of T-cell receptor signaling cascade. This includes phosphorylation of proteins such as Ras GTPase-activating protein (RasGAP) and two RasGAP-associated proteins, p56(dok) and p62(dok).