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| 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). |
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Tyrosine kinase p56lck regulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through tyrosine phosphorylation of IkappaBalpha following hypoxia/reoxygenation. |
| Mahabeleshwar GH, Kundu GC |
| The Journal of biological chemistry. 2003 ; 278 (52) : 52598-52612. |
| PMID 14534291 |
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| 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 |
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| Structure and regulation of Src family kinases. |
| Boggon TJ, Eck MJ |
| Oncogene. 2004 ; 23 (48) : 7918-7927. |
| PMID 15489910 |
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| 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 |
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