LCK / TRP channels
Name: Tyrosine-protein kinase Lck
(LCK)
Official Symbol: LCK
provided by HGNC
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.
Source: Reorganizing the protein space at the Universal Protein Resource (UniProt)
Nucleic Acids Res. 40: D71-D75 (2012).
Species | External DB | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Entrez Gene | UniprotKB | DIP | IntAct | MINT | BioGRID | STRING | IUPHAR-DB | KEGG | OMIM | |
Human
|
3932 | P06239 | DIP-553N | P06239 | MINT-110378 | 110124 | P06239 | hsa:3932 | 153390 | |
Mouse
|
16818 | P06240 | DIP-30988N | P06240 | MINT-85459 | 201120 | P06240 | mmu:16818 | ||
Rat
|
313050 | Q01621 | UNK-5385195 | 260306 | Q01621 | rno:313050 |
PPI pairs:
Biological Process:
- GO:0006919 : activation of cysteine-type endopeptidase activity involved in apoptotic process
- GO:0007568 : aging
- GO:0050853 : B cell receptor signaling pathway
- GO:0006882 : cellular zinc ion homeostasis
- GO:0006917 : induction of apoptosis
- GO:0050900 : leukocyte migration
- GO:0018108 : peptidyl-tyrosine phosphorylation
- GO:0030168 : platelet activation
- GO:0045588 : positive regulation of gamma-delta T cell differentiation
- GO:0010628 : positive regulation of gene expression
- GO:0050862 : positive regulation of T cell receptor signaling pathway
- GO:0042523 : positive regulation of tyrosine phosphorylation of Stat5 protein
- GO:0070474 : positive regulation of uterine smooth muscle contraction
- GO:0046777 : protein autophosphorylation
- GO:0050690 : regulation of defense response to virus by virus
- GO:0051209 : release of sequestered calcium ion into cytosol
- GO:0042493 : response to drug
- GO:0042542 : response to hydrogen peroxide
- GO:0009612 : response to mechanical stimulus
- GO:0010043 : response to zinc ion
- GO:0031295 : T cell costimulation
- GO:0030217 : T cell differentiation
- GO:0050852 : T cell receptor signaling pathway
- GO:0016032 : viral reproduction
- GO:0019048 : virus-host interaction
Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/
World Wide Web URL: http://www.geneontology.org/
Disease:
No information in OMIM
Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine,
Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/
World Wide Web URL: http://omim.org/
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Screening | ||||||||||
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPV4 | LCK | Inference | Prediction | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Validation: In vivo validation | ||||||||||
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPV4 | LCK | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Not used | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top |
Functional consequence | ||||||||||||
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TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPV4 | LCK | Calcium measurement | Activation | 12538589 | ||||||||
TRPV4 | LCK | In vitro PTM assay | Phosphorylation (Tyr-273) | 12538589 |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)