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LCK (lymphocyte-specific protein tyrosine kinase)

Written2005-05Deepak Pralhad Patil, Gopal Chandra Kundu
CSIR-JRF,c/o Dr. G. C. Kundu, National Center for Cell Science, NCCS Complex, Ganeshkhind, Pune(Maharastra)-411007, India

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)P56-LCK LSK (T cell-specific protein-tyrosine kinase)
lck tyrosine kinase (AA 1-142)
membrane associated protein tyrosine kinase
proto-oncogene LCK
protein-tyrosine kinase
put. ptk (135aa); tyrosine kinase
HGNC (Hugo) LCK
HGNC Previous namelymphocyte-specific protein tyrosine kinase
LocusID (NCBI) 3932
Atlas_Id 14
Location 1p35.1  [Link to chromosome band 1p35]
Location_base_pair Starts at 32251265 and ends at 32286165 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping LCK.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
C2CD5 (12p12.1)::LCK (1p35.2)KLC4 (6p21.1)::LCK (1p35.1)LCK (1p35.1)::LCK (1p35.1)
LCK (1p35.1)::TRBV20OR9-2 (-)LCK (1p35.1)::ZNF385D (3p24.3)LCK (1p35.2)::TRBV20OR9-2 (-)

DNA/RNA

 
Description DNA sequence is located on chromosome no.1 on the arm 1(p).
Transcription Consists of 13 exons and 12 introns spanning 12.3 kb.
Pseudogene Unknown

Protein

 
Description The kinase p56lck (509 aa) is a T-lymphocyte-specific member of the Src family of non-receptor protein tyrosine kinase. Lck is a 56 kDa phosphoprotein expressed in variety of lymphoid and non-lymphoid cell lineages. Lck contain myristylation sequence, unique amino-terminal regions, followed by Src homology domains SH3 and SH2, a tyrosine kinase catalytic domain, and C-terminal regulatory domain. Lck associates with the inner face of the plasma membrane through its amino-terminus. This interaction is mediated by both myristic acid and palmitic acid that are bound to the amino terminal glycine and Cys-3 and/or Cys-5. The Unique region of Lck represents the domain possessing the greatest sequence diversity within this group of enzymes. This domain is thought to be involved in the interaction of the Lck with specific cellular proteins including Lck substrate. In T-cells it is known, to mediate association with the cytoplasmic tail of T-cell coreceptors CD4 and CD8a. SH3 (Src homology 3) domain is mainly implicated in the regulation of protein-protein interactions, recognizing proline-rich region found in guanine nucleotide exchange factors and GTPase activating proteins. SH2 (Src homology 2) domain of Lck recognizes phosphorylated tyrosine residues on other proteins thereby facilitating the formation of tyrosine phosphorylation-induced multimeric complexes. The tyrosine kinase domain is the catalytic domain of Lck catalyzing the transfer of the gamma-phosphate from ATP to tyrosine residues on proteins. The catalytic domain contains a site of autophosphorylation (Tyr-394), which plays an important role in regulating the protein kinase activity. A C-terminal regulatory domain is also seen containing the major site of tyrosine phosphorylation in vivo (Tyr-505). Phosphorylation of Csk (C-terminal Src kinase) at Tyr-505 leads to inactivation of Lck. Lck is also activated by oxidative stress. Reoxygenation after hypoxia induces Lck kinase activity.
Expression Expressed in variety of lymphoid and non-lymphoid cell lineages (Breast cancer tissues and other cancers too).
Localisation Cell membrane
Function
  • T-cell development,
  • T-cell activation.
  • Homology Shares sequence homology with other Src family kinases (Src, Hck, Fyn, Blk, Lyn, Fgr, Yes, and Yrk).

    Mutations

    Note Not reported yet

    Implicated in

    Note
      
    Entity Breast cancer, T-cell Leukemia, Colon carcinoma.
    Oncogenesis Upregulation of Lck is seen in many cases of Breast cancer. It is also overexpressed in lymphoma, colon cancer. Rearrangement of LCK gene is also reported in murine lymphoma cell line. Oncogenic activation of Lck due translocation of the LCK gene is reported in the human HSB2 T-cell leukemia with with LCK/ TCRB involvement. Lck regulates cell motility through NF-KB mediated uPA secretion following hypoxia and reoxygenation in Breast cancer.
      
    Disease Type 1 Diabetes
    Prognosis T-cell mediated Type diabetes (Autoimmune disease) shows defect in TCR/CD3-mediated T-cell activation due to the abnormal expression of LCK.
      

    Bibliography

    Structure and regulation of Src family kinases.
    Boggon TJ, Eck MJ
    Oncogene. 2004 ; 23 (48) : 7918-7927.
    PMID 15489910
     
    Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells.
    Foss FM, Veillette A, Sartor O, Rosen N, Bolen JB
    Oncogene research. 1989 ; 5 (1) : 13-23.
    PMID 2476706
     
    Activation of the Lck tyrosine protein kinase by hydrogen peroxide requires the phosphorylation of Tyr-394.
    Hardwick JS, Sefton BM
    Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (10) : 4527-4531.
    PMID 7538674
     
    Tyrosine kinase, p56lck-induced cell motility, and urokinase-type plasminogen activator secretion involve activation of epidermal growth factor receptor/extracellular signal regulated kinase pathways.
    Mahabeleshwar GH, Das R, Kundu GC
    The Journal of biological chemistry. 2004 ; 279 (11) : 9733-9742.
    PMID 14699120
     
    Specific deficiency of p56lck expression in T lymphocytes from type 1 diabetic patients.
    Nervi S, Atlan-Gepner C, Kahn-Perles B, Lecine P, Vialettes B, Imbert J, Naquet P
    Journal of immunology (Baltimore, Md. : 1950). 2000 ; 165 (10) : 5874-5883.
    PMID 11067948
     
    lck suppresses gene expression from various promoters including human T-cell leukemia virus type I promoter.
    Ohta M, Morita T, Shimotohno K
    Japanese journal of cancer research : Gann. 1990 ; 81 (5) : 440-444.
    PMID 2116390
     
    Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.
    Palacios EH, Weiss A
    Oncogene. 2004 ; 23 (48) : 7990-8000.
    PMID 15489916
     

    Citation

    This paper should be referenced as such :
    Patil, DP ; Kundu, GC
    LCK (lymphocyte-specific protein tyrosine kinase)
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):229-230.
    Free journal version : [ pdf ]   [ DOI ]


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
      dic(9;12)(p13;p13) PAX5::ETV6
    Pediatric T-Cell Acute Lymphoblastic Leukemia
    t(1;7)(p34;q34) TRB::LCK
    t(2;5)(p23;q35) SQSTM1::ALK
    t(5;9)(q35;q34) SQSTM1::NUP214
    T-lineage acute lymphoblastic leukemia (T-ALL)


    External links

    Nomenclature
    HGNC (Hugo)LCK   6524
    LRG (Locus Reference Genomic)LRG_153
    Cards
    AtlasLCKID14ch1p34
    Entrez_Gene (NCBI)LCK    LCK proto-oncogene, Src family tyrosine kinase
    AliasesIMD22; LSK; YT16; p56lck; 
    pp58lck
    GeneCards (Weizmann)LCK
    Ensembl hg19 (Hinxton)ENSG00000182866 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000182866 [Gene_View]  ENSG00000182866 [Sequence]  chr1:32251265-32286165 [Contig_View]  LCK [Vega]
    ICGC DataPortalENSG00000182866
    TCGA cBioPortalLCK
    AceView (NCBI)LCK
    Genatlas (Paris)LCK
    SOURCE (Princeton)LCK
    Genetics Home Reference (NIH)LCK
    Genomic and cartography
    GoldenPath hg38 (UCSC)LCK  -     chr1:32251265-32286165 +  1p35.2   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)LCK  -     1p35.2   [Description]    (hg19-Feb_2009)
    GoldenPathLCK - 1p35.2 [CytoView hg19]  LCK - 1p35.2 [CytoView hg38]
    ImmunoBaseENSG00000182866
    Genome Data Viewer NCBILCK [Mapview hg19]  
    OMIM153390   615758   
    Gene and transcription
    Genbank (Entrez)AA747421 AF228313 AJ865079 AK098027 AK303073
    RefSeq transcript (Entrez)NM_001042771 NM_001330468 NM_005356
    Consensus coding sequences : CCDS (NCBI)LCK
    Gene ExpressionLCK [ NCBI-GEO ]   LCK [ EBI - ARRAY_EXPRESS ]   LCK [ SEEK ]   LCK [ MEM ]
    Gene Expression Viewer (FireBrowse)LCK [ Firebrowse - Broad ]
    GenevisibleExpression of LCK in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)3932
    GTEX Portal (Tissue expression)LCK
    Human Protein AtlasENSG00000182866-LCK [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Conserved Domain (NCBI)LCK
    Human Protein Atlas [tissue]ENSG00000182866-LCK [tissue]
    HPRD01080
    Protein Interaction databases
    BioGRIDLCK
    STRING (EMBL)LCK
    ZODIACLCK
    Ontologies - Pathways
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    EVEXLCK
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Oct 8 21:21:09 CEST 2021

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