Gene content    
LCK ( by HUGO)
Lymphocyte-Specific Protein Tyrosine Kinase
Oncogene
Lymphocyte-Specific Protein Tyrosine Kinase
Leukocyte C-Terminal Src Kinase
Lymphocyte Cell-Specific Protein-Tyrosine Kinase
T Cell-Specific Protein-Tyrosine Kinase
LSK
EC 2.7.10.2
YT16
P56(LSTRA) Protein-Tyrosine Kinase
p56lck
pp58lck
Proto-Oncogene Tyrosine-Protein Kinase LCK
T-Lymphocyte Specific Protein Tyrosine Kinase P56lck
Tyrosine-Protein Kinase Lck
p56-LCK
Protein YT16
Proto-Oncogene Lck
EC 2.7.10
NCBI: 1p34.3    Ensembl: 1p35.1
LCK_HUMANSize: 509 amino acidsMass: 58001 Da

  • Subunit: Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocyte migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70 Mass spectrometry: Mass=57869.42; Method=MALDI; Range=2-509; Source=PubMed:11840567; Sequence caution: Sequence=CAI22320.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAI22321.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for LCK (see all 52): 1BHF (3D) [IMAGE] 1BHH (3D) [IMAGE] 1CWD (3D) [IMAGE] 1CWE (3D) [IMAGE] 1FBZ (3D) [IMAGE] 1H92 (3D) [IMAGE]
  • Tissue specificity: Expressed specifically in lymphoid cells [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays including LCK: Lung Cancer in human mouse rat Apoptosis 384HT in human mouse rat T-cell & B-cell Activation in human mouse rat Primer Products: [IMAGE] OriG
  • Function:
    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
                          
    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
  • Catalytic activity:
    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
  • Similarity:
    Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily
                          
    Contains 1 protein kinase domain
                          
    Contains 1 SH2 domain
                          
    Contains 1 SH3 domain [IMAGE]
  • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR000719Prot_kinase_domProtein kinaseDomain
    IPR000980SH2SH2 motifDomain
    IPR001245Ser-Thr/Tyr_kinase_cat_domTyrosine protein kinaseDomain
    IPR001452SH3_domainSH3Domain
    IPR008266Tyr_kinase_ASTyrosine protein kinase, active siteActive Sites
    IPR011009Kinase-like_domProtein kinase-likeDomain
    BlocksIPB000980SH2 domain signatureSH2 domain signature
    IPB001452SH3 domain signatureSH3 domain signature
    IPB008266Tyrosine protein kinaseTyrosine protein kinase, active site

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process activation of cysteine-type endopeptidase activity involved in apoptotic process IDA GOA 16116473
    cellular zinc ion homeostasis IEP GOA 11739864
    dephosphorylation IDA GOA 8506364
    hemopoiesis NAS GOA 12884910
    positive regulation of T cell activation IDA GOA 8943371
    positive regulation of T cell receptor signaling pathway NAS GOA 12614355
    protein phosphorylation IDA GOA 214242
    regulation of lymphocyte activation NAS GOA 7852312
    response to drug IDA GOA 16116473
    T cell differentiation IMP GOA 1579166
    Cellular Component membrane raft IDA GOA 12150984
    pericentriolar material IDA GOA 7513706
    plasma membrane IDA GOA 12150984
    Molecular Function ATPase binding IPI GOA 15671290
    CD4 receptor binding IPI GOA 7486703
    CD8 receptor binding IPI GOA 2470098
    glycoprotein binding IPI GOA 14625311
    identical protein binding IPI GOA 17118402
    phosphatidylinositol 3-kinase binding IPI GOA 7504174
    protein binding IPI GOA 10209036
    protein C-terminus binding IPI GOA 16245368
    protein kinase binding IPI GOA 8618896
    protein serine/threonine phosphatase activity IDA GOA 8506364
    protein tyrosine kinase activity IDA GOA 214242
    SH2 domain binding IPI GOA 7852312

    Disorder & Mutation    
    Source Disease
    SWISS-PROTNote=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB

    LCK cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene