Lck 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. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. 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. 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. 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Expressed specifically in lymphoid cells. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); Src family; TK group
Chromosomal Location of Human Ortholog: 1p35.2
Cellular Component:  cytosol; immunological synapse; membrane raft; pericentriolar material; plasma membrane
Molecular Function:  ATP binding; ATPase binding; CD4 receptor binding; CD8 receptor binding; identical protein binding; phosphatidylinositol 3-kinase binding; phosphotyrosine residue 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; T cell receptor binding
Biological Process:  activation of cysteine-type endopeptidase activity involved in apoptotic process; cellular zinc ion homeostasis; hemopoiesis; leukocyte migration; peptidyl-tyrosine phosphorylation; platelet activation; positive regulation of heterotypic cell-cell adhesion; positive regulation of intrinsic apoptotic signaling pathway; positive regulation of leukocyte cell-cell adhesion; positive regulation of protein kinase B signaling; positive regulation of T cell activation; positive regulation of T cell receptor signaling pathway; protein dephosphorylation; protein phosphorylation; regulation of defense response to virus by virus; regulation of lymphocyte activation; release of sequestered calcium ion into cytosol; response to drug; T cell costimulation; T cell differentiation; T cell receptor signaling pathway
Disease: Immunodeficiency 22
Reference #:  P06239 (UniProtKB)
Alt. Names/Synonyms: LCK; LSK; Lymphocyte cell-specific protein-tyrosine kinase; lymphocyte-specific protein tyrosine kinase; p56(LSTRA) protein-tyrosine kinase; p56-LCK; p56lck; pp58lck; Proto-oncogene Lck; proto-oncogene tyrosine-protein kinase LCK; T cell-specific protein-tyrosine kinase; T-lymphocyte specific protein tyrosine kinase p56lck; Tyrosine-protein kinase Lck; YT16
Gene Symbols: LCK
Molecular weight: 58,001 Da
Basal Isoelectric point: 5.23  Predict pI for various phosphorylation states
CST Pathways:  GPCR Signaling to MAPKs  |  T Cell Receptor Signaling  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein