Summary

Name LCK
Full Name Tyrosine-protein kinase Lck
Synonyms 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
Primary ID P06239
Links - -
Type protein
Relations 89
Pathways P38 Signaling, T cell activation, Glucocorticoid Receptor
Inhibitors CCT239065
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 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 (PubMed:27335501).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation LCK 0.30
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ img/unknown.png phosphorylation LCK
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation LCK 0.19
Publications: 1 Organism: In Vitro
Pathways:T cell activation
+ down-regulates img/direct_inhibition.png phosphorylation LCK 0.15
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.15
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.30
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ up-regulates activity img/direct-activation.png phosphorylation MUC1 0.10
Publications: 2 Organism: , Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ACP1 0.27
Publications: 2 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation DEF6 0.20
Publications: 3 Organism: Homo Sapiens, In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation DAPP1 0.13
Publications: 1
+ img/unknown.png phosphorylation VAV1 0.58
Publications: 3 Organism: In Vitro
+ img/unknown.png phosphorylation EZR 0.23
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation ZAP70 0.86
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling, T cell activation
+ up-regulates activity img/direct-activation.png phosphorylation CD3E 0.60
Publications: 2 Organism: Chlorocebus Aethiops
Pathways:T cell activation
+ up-regulates img/direct-activation.png phosphorylation CD28 0.54
Publications: 2 Organism: Homo Sapiens
Pathways:T cell activation
+ down-regulates activity img/direct_inhibition.png phosphorylation LCK 0.50
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation LAT 0.64
Publications: 2 Organism: Homo Sapiens
Pathways:T cell activation
+ down-regulates activity img/direct_inhibition.png phosphorylation CTLA4 0.07
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK3 0.30
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ img/unknown.png phosphorylation CTLA4 0.07
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SH2B3 0.22
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PRKCD 0.36
Publications: 3 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation PTEN 0.04
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation, binding ZAP70 0.86
Publications: 7 Organism: Mus Musculus, Homo Sapiens, In Vitro
Pathways:P38 Signaling, T cell activation
+ up-regulates img/direct-activation.png phosphorylation CD33 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation FOXP3 0.07
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation IL2RB 0.25
Publications: 5 Organism: In Vitro
+ down-regulates img/direct_inhibition.png dephosphorylation LCK 0.24
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation LCK
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor, P38 Signaling, T cell activation
+ down-regulates activity img/direct_inhibition.png dephosphorylation LCK
Publications: 2 Organism: Homo Sapiens, Mus Musculus
+ down-regulates activity img/direct_inhibition.png dephosphorylation LCK
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation LCK
Publications: 2 Organism: Homo Sapiens
Pathways:T cell activation
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKBIA 0.21
Publications: 1
Pathways:T cell activation
+ img/unknown.png phosphorylation LCP2 0.45
Publications: 2 Organism: In Vitro
Pathways:T cell activation
+ up-regulates activity img/direct-activation.png phosphorylation SHC1 0.52
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CD5 0.28
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation ZAP70 0.86
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling, T cell activation
+ down-regulates img/direct_inhibition.png phosphorylation LCK 0.48
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ITK 0.58
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation PTPN6 0.45
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.04
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PTPN6 0.45
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SIGLEC10 0.17
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MED28 0.16
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PIK3R1 0.53
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:T cell activation
+ down-regulates activity img/direct_inhibition.png phosphorylation PI3K
Publications: 1 Organism: Chlorocebus Aethiops
+ img/unknown.png phosphorylation SIGLEC10 0.17
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ADAM15 0.28
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PLCG2 0.30
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PRKCQ 0.40
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DOK1 0.34
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TCR
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ down-regulates img/direct_inhibition.png chemical inhibition LCK
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png dephosphorylation LCK 0.18
Publications: 1 Organism: Homo Sapiens
Tissue: Brain, Kidney
+ up-regulates img/direct-activation.png binding LCK
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ up-regulates activity img/direct-activation.png binding LCK 0.08
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates img/indirect-activation.png unknown MAPK1 0.15
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ up-regulates img/direct-activation.png phosphorylation CD247 0.73
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates img/direct-activation.png binding NOTCH1 0.08
Publications: 1 Organism: Homo Sapiens