LCK

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 different isoforms have been described. [provided by RefSeq, Aug 2016]LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase) is a Protein Coding gene. Diseases associated with LCK include Immunodeficiency 22 and Cd45 Deficiency. Among its related pathways are T cell receptor signaling pathway and NF-kappa B signaling pathway. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is HCK.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 tyrosine 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. Interacts with FYB2 (PubMed:27335501).

LCK

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 tyrosine 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. Interacts with FYB2 (PubMed:27335501).

Activation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
B cell receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cellular zinc ion homeostasisManual Assertion Based On ExperimentIEP:UniProtKB
Hemopoiesis1 PublicationNAS:UniProtKB
Innate immune responseManual Assertion Based On ExperimentIBA:GO_Central
Intracellular signal transductionManual Assertion Based On ExperimentIDA:ARUK-UCL
Leukocyte migrationTAS:Reactome
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIMP:ARUK-UCL
Platelet activationTAS:Reactome
Positive regulation of heterotypic cell-cell adhesionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of leukocyte cell-cell adhesionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of T cell activationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of T cell receptor signaling pathway1 PublicationNAS:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of lymphocyte activation1 PublicationNAS:UniProtKB
Release of sequestered calcium ion into cytosolISS:UniProtKB
Response to xenobiotic stimulusManual Assertion Based On ExperimentIDA:UniProtKB
T cell costimulationTAS:Reactome
T cell differentiationManual Assertion Based On ExperimentIMP:UniProtKB
T cell receptor signaling pathwayTAS:Reactome
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central

Cell membrane
Cytoplasm, cytosol
Present in lipid rafts in an inactive form.

A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
Immunodeficiency 22 (IMD22):
A primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive.

Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell receptor signaling.
Myristoylation is required prior to palmitoylation.
Palmitoylation regulates association with the plasma membrane and could be mediated by ZDHHC2.