Lck, active

Lck, active

Upstate (Millipore)

10 µg

N-terminal His6-tagged, recombinant full-length human Lck

Kinase Assay

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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.

FUNCTION: SwissProt: P06239 # Tyrosine kinase that 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.


SIZE: 509 amino acids; 58001 Da

SUBUNIT: 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 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.

SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note=Present in lipid rafts in an unactive form.

TISSUE SPECIFICITY: Expressed specifically in lymphoid cells.


DOMAIN: SwissProt: P06239 The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.

PTM: Phosphorylated on Tyr-394, which increases enzymatic activity (By similarity). Phosphorylated on Tyr-505, which decreases activity.
DISEASE:SwissProt: P06239 # A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.

SIMILARITY: 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.

Human

59kDa

routinely evaluated by phosphorylation of Src substrate peptide

Upstate

expressed in Sf21 insect cells

Lck

P06239

For Specific Activity data, refer to the Certificate of Analysis for individual lots of this enzyme.

6 months at -70C

TK

This enzyme is part of KinaseProfiler™, a custom inhibitor selectivity discovery service.

Also available in 250 µg size --call for pricing and availability and reference catalog number 14-442M when ordering the 250 µg size.

Lck is a lymphocyte-specific member of the Src-family of non-receptor tyrosine kinases. Lck is activated by the phosphatase CD45, which dephosphorylates the c-terminal inhibitory Tyrosine of Lck. Lck signals by phosphorylating the ITAM motif on the T-cell Receptor, which allows for recruitment and activation of ZAP-70, essential for T-cell activation.

• LCK
• p56lck
• YT16
• pp58lck
• p56-LCK
• LSK

• Kinases
• Signal Transduction

Lck, active

• NM_001042771.1
• NM_005356.3

Ni²⁺/NTA-agarose