Recombinant Human Tyrosine-protein kinase Lck (LCK)

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 (PubMed:2470098). Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways (PubMed:2470098). Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors (PubMed:2470098). 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 (PubMed:2470098). LCK then phosphorylates tyrosine 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 (PubMed:2470098, PubMed:40592325). 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. Interacts with FYB2 (PubMed:27335501)

Subcellular Location

Cell membrane (Lipid-anchor); Cytoplasm, cytosol

Disease Association

[A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB] | Immunodeficiency 22 (IMD22) : A primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed specifically in lymphoid cells

Subunit

(Microbial infection) Interacts with HIV-1 Nef through its SH3 domain

• Koga Y. et al. A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases. — Eur. J. Immunol. (1986)
• Perlmutter R.M. et al. Structure and expression of lck transcripts in human lymphoid cells. — J. Cell. Biochem. (1988)
• Rouer E. et al. Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons. — Gene (1989)
• Wright D.D. et al. Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. — Mol. Cell. Biol. (1994)
• Vogel L.B. et al. An aberrant lck mRNA in two human T-cell lines. — Biochim. Biophys. Acta (1995)
• Nervi S. et al. No association between lck gene polymorphisms and protein level in type 1 diabetes. — Diabetes (2002)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)