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Symbol LCK contributors: mct/pgu - updated : 16-02-2016
HGNC name lymphocyte-specific protein tyrosine kinase
HGNC id 6524
Corresponding disease
IMD22 Immunodeficiency 22
Location 1p35.2      Physical location : 32.716.839 - 32.751.765
Synonym name
  • proto-oncogene tyrosine-protein kinase LCK
  • p56(LSTRA) protein-tyrosine kinase
  • T cell-specific protein-tyrosine kinase
  • Synonym symbol(s) RP4-675E8.4, LSK, YT16, p56lck, pp58lck
    TYPE functioning gene
    STRUCTURE 34.93 kb     13 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    text long and short isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2118 - 509 - 2011 21339332
    13 - 2135 - 509 - 2011 21339332
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly Homo sapiens
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • a SH3, controling T lymphocyte activation by regulating MAPK pathway induction
  • a SH2 domains mediating interaction with SQSTM1, interaction regulated by ser-58 phosphorylation
  • a kinase domain alone is sufficient to bind SOCS1
  • protein kinase superfamily
  • Tyr protein kinase family
  • SRC subfamily
  • CATEGORY protooncogene
        plasma membrane
  • may be recruited to the plasma membrane by RHOH, which also binds CSK, resulting in LCK inactivation
  • oncogenic LCK kinase translocates to the nucleus and binds to the LMO2 gene promoter
  • basic FUNCTION
  • playing an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function
  • plays a key role in targeting HIV-1 Gag to the plasma membrane in T cells
  • protects cells from glucocorticoid-induced apoptosis and its inhibition enhances sensitivity to dexamethasone
  • role for LCK in the regulation of Th2-type immunity
  • plays essential roles in development, antigen-induced T cell activation, and proliferation
  • essential for activation of mature T cells
  • non-receptor tyrosine kinase, critically involved in fractionated radiation-induced expansion of the glioma-initiating cell population and decreased cellular sensitivity to anticancer treatments
  • LCK signaling is required, at the immunological synapse, for the centrosome to dock at the plasma membrane
  • plays a key role in T cell signal transduction and is tightly regulated by phosphorylation and dephosphorylation
  • oncogenic LCK can initiate multiple signaling cascades that are likely to be controlled by the spatial localization of the oncoprotein
  • regulation of the cellular location and activation of LCK in maturing thymocytes is a key regulatory mechanism to prevent T-cell responses to self-antigens
  • major role for LCK in proximal and distal B-cell receptor-mediated signaling in chronic lymphocytic leukemia cells
  • mediates ITGB1 signalling to regulate Schwann cell migration and myelination
  • plays a crucial role in the T-cell response by transducing early activation signals triggered by TCR (T-cell receptor) engagement
  • T cell receptor (TCR) phosphorylation requires the kinase LCK and phosphatase PTPRC
  • LCK, which plays a unique role in enforcing MHC restriction, is essential for thymic development in presence or absence of CBL, ensuring MHC restriction of T cells derived from either pathway
  • is an Src family kinases (SFKs) that is central to the initiation of T cell activation in response to ligand binding to the T cell receptor (TCR) and is also critical for later signaling processes
  • kinase activity of LCK requires both the phosphorylation of an activating tyrosine residue and the dephosphorylation of an inhibitory tyrosine residue
  • kinase activity of ZAP70 stimulates negative feedback pathways that target LCK and thereby modulate the phosphorylation patterns of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 and zeta chain components of the TCR
  • novel function of nuclear LCK in promoting human leukemic T cell survival through interaction with a tumor suppressor
  • is a key T-cell kinase and widely implicated in blood malignancies
  • role of mitochondrial LCK in metabolic reprogramming of leukemic cells
  • CELLULAR PROCESS cell life, proliferation/growth
    text T cell development and function
    signaling signal transduction
    RAS signaling pathway
    a component
  • ITGB2/LCK/ZAP70 complex is in position to initiate the rapid adhesion strengthening and migration necessary for T-lymphocyte responses when stimulated vasculature is encountered at sites of infection or injury
    small molecule nucleotide,
  • ATP
  • protein
  • mediating phosphorylation of DOK proteins
  • interaction between PRKD2 and LCK (LCK regulated the activity of PRKD2 by tyrosine phosphorylation, which in turn may have modulated the physiological functions of PKD2 during TCR-induced T cell activation)
  • anchoring CD4 to lipid microdomains (rafts) on microvilli
  • interacts with RASSF5 through its C-terminal Src homology 2 binding motif and LCK-mediated phosphorylation is critical for the efficient translocation of RASSF5 into the nuclear compartment
  • SH2D2A through its interaction with both ITK and LCK, primes ITK for LCK mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements
  • RHOH binds and modulates LCK, the non-receptor tyrosine kinase crucial in initiating pre-TCR and TCR signallings
  • LAT promotes TCR signal initiation, suggesting that this adaptor may contribute to maintain active LCK in proximity of their substrates
  • ITGB2 is constitutively associated with the protein tyrosine kinases LCK and ZAP70
  • oncogenic LCK may activate LMO2 promoter through direct interaction
  • oncogenic LCK and JAK2 may utilize different mechanisms to upregulate LMO2 levels during oncogenic transformation
  • DLG1, which acts as a scaffold for many signaling molecules including the TCR and LCK, could mediate the cellular redistribution of LCK during T-cell maturation
  • upregulates FOXP3 by tyrosine phosphorylation, resulting in decreased MMP9, SKP2, and VEGFA expression, and suppressed cellular invasion
  • PTK2 negatively regulates LCK function downstream of the T cell antigen receptor
  • spatial regulation of LCK by PTPRC and GM1 ganglioside determines the outcome of apoptotic response to LGALS1 and this local regulation may occur only upon intimate effector (LGALS1 expressing) cell-T-cell attachment
  • prominent immunoregulatory function of LGALS1, is induction of apoptosis in activated T-cells by a process depending on the activity of SRC family tyrosine kinase, LCK
  • both SLAMF6-associated LCK phosphorylation and kinase activity were enhanced in restimulated T cells, amplifying proximal TCR signaling
  • SH2D1A facilitates recruitment and activation of LCK at SLAMF6 receptors during restimulation-induced cell death
  • IGF2R specifically controls the balance between active and inactive LCK in resting T cells, which guarantees operative T cell effector functions
  • in T-cells, cholesterol-dependent membrane domains function in the regulation of the Src family kinase LCK by sequestering LCK from its activator PTPRC
  • in a kinase-independent manner, mitochondrial LCK interferes with mitochondrial translational machinery through competitive binding to GADD45GIP1
  • cell & other
  • membrane associated
    inhibited by negatively regulated by CB1 ubiquitin ligase
    SOCS6 (negative regulator of LCK)
    repressed by dexamethasone that downregulates LCK, which, in turn, suppresses lymphocyte activation by inhibiting pro-survival calcium oscillations
    Other regulated by SOCS1 (important role of SOCS in regulating LCK functions)
    corresponding disease(s) IMD22
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    breakpoint in T-cell acute lymphoblastic leukemia with translocations t(1;7)(p34;q34
    constitutional     --low  
    in one case of SCID(severe combined immunodeficiency)
    tumoral     --over  
    in lymphomas of germinal center origin (e.g. follicular lymphoma) and also many mantle cell lymphomas, chronic lymphocytic leukemia (CLL) and most T-cell neoplasms
    Variant & Polymorphism
    Candidate gene
    Therapy target
    small-molecule inhibitors of Lck, such as dasatinib, may function to reverse glucocorticoid resistance in some lymphoid malignancies