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Gene Review

LCK  -  LCK proto-oncogene, Src family tyrosine...

Homo sapiens

Synonyms: IMD22, LSK, Leukocyte C-terminal Src kinase, Lymphocyte cell-specific protein-tyrosine kinase, Protein YT16, ...
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Disease relevance of LCK


High impact information on LCK


Chemical compound and disease context of LCK


Biological context of LCK


Anatomical context of LCK

  • However, in this report, we now demonstrate that neither LCK nor FYN are obligatory for IL-2-induced growth of HTLV-I-infected human T cells [10].
  • Ligation of the CD2 cell surface glycoprotein expressed on T lymphocytes and NK cells induces protein tyrosine phosphorylation and activation of the Src kinases, LCK and FYN [13].
  • Interleukin 4 inhibits IL-2-induced proliferation of a human T-leukemia cell line without interfering with p56-LCK kinase activation [12].
  • These findings thus imply the existence of other signal-transducing molecules, besides p56-LCK, that physically participate in IL-2R complexes and that are necessary for initiation of the biochemical events ultimately responsible for IL-2's pleiotropic actions on lymphocytes [14].
  • In conclusion, CD8alpha down-regulates the production of major Th2-type cytokines, in part mediated by LCK and/or linker for activation of T cells, and may induce differentiation of tumor-specific Th1 cells, which makes this coreceptor an interesting candidate to improve the clinical potential of TCR gene transfer to treat cancer [15].

Associations of LCK with chemical compounds

  • Furthermore, when cultured in the absence of IL-2, transfected T cells whose relative levels of p56-LCK activity were elevated by approximately 20-50-fold died with the same kinetics as control cells and underwent apoptosis, as defined by uptake of trypan blue dye and DNA fragmentation assays, respectively [14].
  • ZAP-70 becomes phosphorylated and activated by LCK protein tyrosine kinase after interaction of its two NH2-terminal SH2 domains with tyrosine-phosphorylated subunits of the activated TCR [16].
  • The IC(50) for LCK inhibition by imatinib was 0.6 muM to 0.8 muM in an in vitro tyrosine kinase assay [17].
  • These results, therefore, suggested that nocodazole prevented initial phosphorylation of the TCR by LCK after stimulation, and as a result, it blocked activation of downstream signaling pathways [18].
  • The introduction of a mutated cysteine motif in CD8alpha, which prevents its binding to LCK and linker for activation of T cells, did not adversely affect expression and T cell cytotoxicity, but counteracted the CD8alpha-mediated down-regulation of IL-4 and IL-5, but not IL-10 [15].

Enzymatic interactions of LCK


Regulatory relationships of LCK

  • Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK tyrosine kinase and facilitates radiation-induced apoptosis [20].

Other interactions of LCK


Analytical, diagnostic and therapeutic context of LCK


  1. Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. Wright, D.D., Sefton, B.M., Kamps, M.P. Mol. Cell. Biol. (1994) [Pubmed]
  2. The differential expression of LCK and BAFF-receptor and their role in apoptosis in human lymphomas. Paterson, J.C., Tedoldi, S., Craxton, A., Jones, M., Hansmann, M.L., Collins, G., Roberton, H., Natkunam, Y., Pileri, S., Campo, E., Clark, E.A., Mason, D.Y., Marafioti, T. Haematologica (2006) [Pubmed]
  3. Absence of transcription of lck (lymphocyte specific protein tyrosine kinase) message in IL-2-independent, HTLV-I-transformed T cell lines. Koga, Y., Oh-Hori, N., Sato, H., Yamamoto, N., Kimura, G., Nomoto, K. J. Immunol. (1989) [Pubmed]
  4. Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia. Tycko, B., Smith, S.D., Sklar, J. J. Exp. Med. (1991) [Pubmed]
  5. Molecular analysis of the T-cell acute lymphoblastic leukemia-associated t(1;7)(p34;q34) that fuses LCK and TCRB. Burnett, R.C., Thirman, M.J., Rowley, J.D., Diaz, M.O. Blood (1994) [Pubmed]
  6. Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor. Weber, J.R., Bell, G.M., Han, M.Y., Pawson, T., Imboden, J.B. J. Exp. Med. (1992) [Pubmed]
  7. Altered lipid raft-associated signaling and ganglioside expression in T lymphocytes from patients with systemic lupus erythematosus. Jury, E.C., Kabouridis, P.S., Flores-Borja, F., Mageed, R.A., Isenberg, D.A. J. Clin. Invest. (2004) [Pubmed]
  8. Aggregation of lipid rafts accompanies signaling via the T cell antigen receptor. Janes, P.W., Ley, S.C., Magee, A.I. J. Cell Biol. (1999) [Pubmed]
  9. The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein. Yoshida, H., Koga, Y., Moroi, Y., Kimura, G., Nomoto, K. Int. Immunol. (1992) [Pubmed]
  10. Neither the LCK nor the FYN kinases are obligatory for IL-2-mediated signal transduction in HTLV-I-infected human T cells. Mills, G.B., Arima, N., May, C., Hill, M., Schmandt, R., Li, J., Miyamoto, N.G., Greene, W.C. Int. Immunol. (1992) [Pubmed]
  11. P56lck A lymphocyte specific protein tyrosine kinase: activation, regulation and signal transduction. Fischer, S., Marie-Cardine, A., Ramos-Morales, F., Bougeret, C., Soula, M., Maridonneau-Parini, I., Benarous, R. Cell. Mol. Biol. (Noisy-le-grand) (1994) [Pubmed]
  12. Interleukin 4 inhibits IL-2-induced proliferation of a human T-leukemia cell line without interfering with p56-LCK kinase activation. Torigoe, T., O'Connor, R., Fagard, R., Fischer, S., Santoli, D., Reed, J.C. Cytokine (1992) [Pubmed]
  13. CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. King, P.D., Sadra, A., Han, A., Liu, X.R., Sunder-Plassmann, R., Reinherz, E.L., Dupont, B. Int. Immunol. (1996) [Pubmed]
  14. Gene transfer investigations of p56-LCK function in IL-2-dependent T-cell lines: implications for mechanisms of IL-2-signal transduction. Taichman, R.S., Torigoe, T., Tanaka, S., Miyashita, T., Reed, J.C. Cytokine (1992) [Pubmed]
  15. CD8 alpha coreceptor to improve TCR gene transfer to treat melanoma: down-regulation of tumor-specific production of IL-4, IL-5, and IL-10. Willemsen, R.A., Sebestyén, Z., Ronteltap, C., Berrevoets, C., Drexhage, J., Debets, R. J. Immunol. (2006) [Pubmed]
  16. ZAP-70 protein tyrosine kinase is constitutively targeted to the T cell cortex independently of its SH2 domains. Huby, R.D., Iwashima, M., Weiss, A., Ley, S.C. J. Cell Biol. (1997) [Pubmed]
  17. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Seggewiss, R., Loré, K., Greiner, E., Magnusson, M.K., Price, D.A., Douek, D.C., Dunbar, C.E., Wiestner, A. Blood (2005) [Pubmed]
  18. Nocodazole inhibits signal transduction by the T cell antigen receptor. Huby, R.D., Weiss, A., Ley, S.C. J. Biol. Chem. (1998) [Pubmed]
  19. The lymphocyte-specific protein tyrosine kinase p56lck is hyperphosphorylated on serine and tyrosine residues within minutes after activation via T cell receptor or CD2. Danielian, S., Fagard, R., Alcover, A., Acuto, O., Fischer, S. Eur. J. Immunol. (1989) [Pubmed]
  20. Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK tyrosine kinase and facilitates radiation-induced apoptosis. Waddick, K.G., Chae, H.P., Tuel-Ahlgren, L., Jarvis, L.J., Dibirdik, I., Myers, D.E., Uckun, F.M. Radiat. Res. (1993) [Pubmed]
  21. Lymphocyte-specific protein tyrosine kinase is a novel risk gene for Alzheimer disease. Zhong, W., Yamagata, H.D., Taguchi, K., Akatsu, H., Kamino, K., Yamamoto, T., Kosaka, K., Takeda, M., Kondo, I., Miki, T. J. Neurol. Sci. (2005) [Pubmed]
  22. A lymphocyte-specific protein tyrosine kinase, p56lck, regulates the PMA-induced internalization of CD4. Yoshida, H., Koga, Y., Nakamura, K., Kimura, G., Nomoto, K. Biochim. Biophys. Acta (1992) [Pubmed]
  23. The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Barber, E.K., Dasgupta, J.D., Schlossman, S.F., Trevillyan, J.M., Rudd, C.E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  24. Increased ubiquitination and reduced expression of LCK in T lymphocytes from patients with systemic lupus erythematosus. Jury, E.C., Kabouridis, P.S., Abba, A., Mageed, R.A., Isenberg, D.A. Arthritis Rheum. (2003) [Pubmed]
  25. cDNA array analysis identifies thymic LCK as upregulated in moderate murine zinc deficiency before T-lymphocyte population changes. Moore, J.B., Blanchard, R.K., McCormack, W.T., Cousins, R.J. J. Nutr. (2001) [Pubmed]
  26. Localization of Zap70, the gene for a T cell-specific protein tyrosine kinase, to mouse and rat chromosomes by fluorescence in situ hybridization and molecular genetic linkage analyses. Saito, T., Matsuda, Y., Ito, H., Fusaki, N., Hori, T., Yamamoto, T. Mamm. Genome (1997) [Pubmed]
  27. The LCK gene is involved in the t(1;7)(p34;q34) in the T-cell acute lymphoblastic leukemia derived cell line, HSB-2. Burnett, R.C., David, J.C., Harden, A.M., Le Beau, M.M., Rowley, J.D., Diaz, M.O. Genes Chromosomes Cancer (1991) [Pubmed]
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