LCK (lymphocyte-specific protein tyrosine kinase)
2005-05-01 Deepak Pralhad Patil , Gopal Chandra Kundu AffiliationCSIR-JRF,c\\\/o Dr. G. C. Kundu, National Center for Cell Science, NCCS Complex, Ganeshkhind, Pune(Maharastra)-411007, India
Identity
HGNC
LOCATION
1p35.1
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
IMD22,LSK,YT16,p56lck,pp58lck
FUSION GENES
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
Proteins
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
Mutations
Note
Not reported yet
Implicated in
Entity name
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 t(1;7)(p34;q34) 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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15489910 | 2004 | Structure and regulation of Src family kinases. | Boggon TJ et al |
| 2476706 | 1989 | Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells. | Foss FM et al |
| 7538674 | 1995 | Activation of the Lck tyrosine protein kinase by hydrogen peroxide requires the phosphorylation of Tyr-394. | Hardwick JS et al |
| 14699120 | 2004 | 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 et al |
| 11067948 | 2000 | Specific deficiency of p56lck expression in T lymphocytes from type 1 diabetic patients. | Nervi S et al |
| 2116390 | 1990 | lck suppresses gene expression from various promoters including human T-cell leukemia virus type I promoter. | Ohta M et al |
| 15489916 | 2004 | Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. | Palacios EH et al |
Other Information
Locus ID:
NCBI: 3932
MIM: 153390
HGNC: 6524
Ensembl: ENSG00000182866
Variants:
dbSNP: 3932
ClinVar: 3932
TCGA: ENSG00000182866
COSMIC: LCK
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36420648 | 2023 | LCK, FOXC1 and hsa-miR-146a-5p as potential immune effector molecules associated with rheumatoid arthritis. | 1 |
| 37370140 | 2023 | LCK facilitates DNA damage repair by stabilizing RAD51 and BRCA1 in the nucleus of chemoresistant ovarian cancer. | 5 |
| 37686072 | 2023 | Identification of Breast Cancer LCK Proto-Oncogene as a Master Regulator of TNBC Neutrophil Enrichment and Polarization. | 1 |
| 38100037 | 2023 | A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature. | 1 |
| 38112969 | 2023 | Combined Immunodeficiency Caused by a Novel Nonsense Mutation in LCK. | 1 |
| 36420648 | 2023 | LCK, FOXC1 and hsa-miR-146a-5p as potential immune effector molecules associated with rheumatoid arthritis. | 1 |
| 37370140 | 2023 | LCK facilitates DNA damage repair by stabilizing RAD51 and BRCA1 in the nucleus of chemoresistant ovarian cancer. | 5 |
| 37686072 | 2023 | Identification of Breast Cancer LCK Proto-Oncogene as a Master Regulator of TNBC Neutrophil Enrichment and Polarization. | 1 |
| 38100037 | 2023 | A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature. | 1 |
| 38112969 | 2023 | Combined Immunodeficiency Caused by a Novel Nonsense Mutation in LCK. | 1 |
| 35558082 | 2022 | Role of Programmed Cell Death Protein-1 and Lymphocyte Specific Protein Tyrosine Kinase in the Aryl Hydrocarbon Receptor- Mediated Impairment of the IgM Response in Human CD5(+) Innate-Like B Cells. | 1 |
| 36078131 | 2022 | A Cysteine Residue within the Kinase Domain of Zap70 Regulates Lck Activity and Proximal TCR Signaling. | 2 |
| 35558082 | 2022 | Role of Programmed Cell Death Protein-1 and Lymphocyte Specific Protein Tyrosine Kinase in the Aryl Hydrocarbon Receptor- Mediated Impairment of the IgM Response in Human CD5(+) Innate-Like B Cells. | 1 |
| 36078131 | 2022 | A Cysteine Residue within the Kinase Domain of Zap70 Regulates Lck Activity and Proximal TCR Signaling. | 2 |
| 33562083 | 2021 | A Novel, LAT/Lck Double Deficient T Cell Subline J.CaM1.7 for Combined Analysis of Early TCR Signaling. | 4 |
Citation
Deepak Pralhad Patil ; Gopal Chandra Kundu
LCK (lymphocyte-specific protein tyrosine kinase)
Atlas Genet Cytogenet Oncol Haematol. 2005-05-01
Online version: http://atlasgeneticsoncology.org/gene/14/lck
