Aliases for LCK Gene
- LCK Proto-Oncogene, Src Family Tyrosine Kinase 2 3
- Lymphocyte Cell-Specific Protein-Tyrosine Kinase 3 4
- Lymphocyte-Specific Protein Tyrosine Kinase 2 3
- T Cell-Specific Protein-Tyrosine Kinase 3 4
- Leukocyte C-Terminal Src Kinase 3 4
- EC 22.214.171.124 4 63
- Lsk 3 4
- T-Lymphocyte Specific Protein Tyrosine Kinase P56lck 3
- Proto-Oncogene Tyrosine-Protein Kinase LCK 3
- P56(LSTRA) Protein-Tyrosine Kinase 3
External Ids for LCK Gene
Previous GeneCards Identifiers for LCK Gene
This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. It contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to the plasma membrane and pericentrosomal vesicles, and binds to cell surface receptors, including CD4 and CD8, and other signaling molecules. Multiple alternatively spliced variants, encoding the same protein, have been described. [provided by RefSeq, Jul 2008]
GeneCards Summary for LCK Gene
LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase) is a Protein Coding gene. Diseases associated with LCK include immunodeficiency 22 and severe combined immunodeficiency due to lck deficiency. Among its related pathways are PI-3K cascade and PI-3K cascade. GO annotations related to this gene include identical protein binding and protein C-terminus binding. An important paralog of this gene is ABL2.
UniProtKB/Swiss-Prot for LCK Gene
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.
Src kinases consist of eight non-receptor tyrosine kinases (Src, Fyn, Yes, Lck, Lyn, Hck, Fgr and Blk) that interact with the intracellular domains of growth factor/cytokine receptors, GPCRs and integrins. Members of the Src kinase family have a very similar domain structure with a high degree of homology in the SH1 (catalytic), linker, SH2 (p-Tyr binding), SH3 (protein-protein interaction) and SH4 (membrane association) domains. c-Src, Fyn and Yes are ubiquitously expressed, although high levels of c-Src are found in platelets, neural tissue and osteoclasts. For c-Src, autophosphorylation of Tyr418 and dephosphorylation of Tyr530 is required to switch the kinase from the inactive closed formation to the active open formation. c-Src can be inactivated by two kinases, c-Src kinase (CSK) and CSK homologous kinase (CHK), both of which phosphorylate Tyr530 of c-Src. The activity of the Src kinase family can also be regulated by phosphatases (e.g. SHP1), binding to adaptor proteins (e.g. Cbp) and proteasomal degradation. Src kinases are key upstream mediators of both the PI 3-K and MAPK signaling pathways, and have been shown to have important roles in cell proliferation, migration and survival.