Tyrosine-Protein Kinase Lck (LCK) Human Recombinant Protein

This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. It contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to the plasma membrane and pericentrosomal vesicles, and binds to cell surface receptors, including CD4 and CD8, and other signaling molecules. Multiple alternatively spliced variants, encoding the same protein, have been described. [provided by RefSeq, Jul 2008]

Lck: a tyrosine kinase of the Src family that is crucial to antigen-receptor signaling in lymphocytes. plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. 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, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls 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. Binds to the cytoplasmic domain of cell surface receptors, such as CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDC2, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of Sam68 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Overexpression in mice leads to thymic tumors. Aberrant expression is seen in T cell leukemias and colon cancer. The leukemic translocation t(1;7)(p34;q34) has breakpoints at the T cell receptor gene and close to the Lck promoters, can cause increased Lck expression, and in one case, point mutations. A mutated Lck has also been seen in a cell line. One patient with aberrant Lck splicing suffered from SCID-like T cell deficiency. Inhibitor: BMS-279700. Three alternatively spliced isoforms of the human proteinhave been described.

Protein type: EC 2.7.10.2; Oncoprotein; Protein kinase, TK; Kinase, protein; Protein kinase, tyrosine (non-receptor); TK group; Src family

Chromosomal Location of Human Ortholog: 1p34.3

Cellular Component: cytosol; extrinsic to internal side of plasma membrane; immunological synapse; intercellular junction; lipid raft; pericentriolar material; plasma membrane

Molecular Function: ATP binding; ATPase binding; CD4 receptor binding; CD8 receptor binding; glycoprotein binding; identical protein binding; non-membrane spanning protein tyrosine kinase activity; phosphoinositide 3-kinase binding; protein binding; protein C-terminus binding; protein kinase binding; protein phosphatase binding; protein serine/threonine phosphatase activity; protein-tyrosine kinase activity; SH2 domain binding

Biological Process: B cell receptor signaling pathway; blood coagulation; caspase activation; cellular zinc ion homeostasis; epidermal growth factor receptor signaling pathway; fibroblast growth factor receptor signaling pathway; hemopoiesis; innate immune response; leukocyte migration; nerve growth factor receptor signaling pathway; phosphoinositide-mediated signaling; platelet activation; positive regulation of gamma-delta T cell differentiation; positive regulation of T cell activation; positive regulation of T cell receptor signaling pathway; positive regulation of tyrosine phosphorylation of Stat5 protein; protein amino acid dephosphorylation; protein amino acid phosphorylation; regulation of cell proliferation; regulation of defense response to virus by virus; regulation of lymphocyte activation; regulation of regulatory T cell differentiation; release of sequestered calcium ion into cytosol; response to drug; T cell costimulation; T cell differentiation; T cell receptor signaling pathway; transmembrane receptor protein tyrosine kinase signaling pathway; viral reproduction

Disease: Immunodeficiency 22