AAA59503.1
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UniProt Primary Accession #
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UniProt Secondary Accession #
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NCBI Official Full Name
LCK, partial
NCBI Official Synonym Full Names
lymphocyte-specific protein tyrosine kinase
NCBI Protein Information
tyrosine-protein kinase Lck; leukocyte C-terminal Src kinase; p56(LSTRA) protein-tyrosine kinase; t cell-specific protein-tyrosine kinase; proto-oncogene tyrosine-protein kinase LCK; lymphocyte cell-specific protein-tyrosine kinase; T-lymphocyte specific protein tyrosine kinase p56lck
UniProt Protein Name
Tyrosine-protein kinase Lck
UniProt Synonym Protein Names
Leukocyte C-terminal Src kinase; LSK; Lymphocyte cell-specific protein-tyrosine kinase; Protein YT16; Proto-oncogene Lck; T cell-specific protein-tyrosine kinase; p56-LCK
UniProt Synonym Gene Names
UniProt Entry Name
LCK_HUMAN
NCBI Summary for LCK
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]
UniProt Comments for 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. 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 tyrosines 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. Ref.28 Ref.31 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40
Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation: The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation. Ref.41
Subunit structure: Binds to the cytoplasmic domain of cell surface receptors, such as AXL, 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 CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocyte migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70. Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.25 Ref.26 Ref.27 Ref.32
Subcellular location: Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note: Present in lipid rafts in an inactive form. Ref.23
Tissue specificity: Expressed specifically in lymphoid cells.
Domain: The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.
Post-translational modification: Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell receptor signaling. Ref.4 Ref.15 Ref.19 Ref.30 Ref.39Myristoylation is required prior to palmitoylation
By similarity.Palmitoylation regulates subcellular location
By similarity.
Involvement in disease: A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.Contains 1 protein kinase domain.Contains 1 SH2 domain.Contains 1 SH3 domain.
Mass spectrometry: Molecular mass is 57869.42 Da from positions 2 - 509. Determined by MALDI. Ref.24
Sequence caution: The sequence CAI22320.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.The sequence CAI22321.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
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Pathways associated with anti-LCK antibody
Diseases associated with anti-LCK antibody
Organs/Tissues associated with anti-LCK antibody
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