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 111
Pathways Mitochondrial dynamics in T cell exhaustion, P38 Signaling, T cell activation
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
+ img/unknown.png phosphorylation LCK 0.328
Publications: 1 Organism: In Vitro
Pathways:T cell activation
+ img/unknown.png phosphorylation LCK 0.335
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.567
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.55
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MUC1 0.471
Publications: 2 Organism: , Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ACP1 0.362
Publications: 2 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation DEF6 0.512
Publications: 3 Organism: Homo Sapiens, In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation DAPP1 0.632
Publications: 1
+ img/unknown.png phosphorylation VAV1 0.774
Publications: 3 Organism: In Vitro
+ img/unknown.png phosphorylation EZR 0.517
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation ZAP70 0.604
Publications: 2 Organism: Homo Sapiens
Pathways:P38 Signaling, T cell activation
+ up-regulates activity img/direct-activation.png phosphorylation CD3E 0.678
Publications: 3 Organism: Chlorocebus Aethiops, Mus Musculus
Pathways:T cell activation
+ up-regulates img/direct-activation.png phosphorylation CD28 0.743
Publications: 2 Organism: Homo Sapiens
Pathways:T cell activation
+ down-regulates activity img/direct_inhibition.png phosphorylation LCK 0.577
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation LAX1 0.408
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation LAT 0.747
Publications: 2 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation CTLA4 0.737
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK3 0.55
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation CCDC50 0.2
Publications: 3 Organism: Homo Sapiens
+ img/unknown.png phosphorylation CTLA4 0.737
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SSBP3 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SH2B3 0.582
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SH2D2A 0.593
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PRKCD 0.509
Publications: 3 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation PTEN 0.379
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation, binding ZAP70 0.604
Publications: 8 Organism: In Vitro, Mus Musculus, Homo Sapiens
Pathways:P38 Signaling, T cell activation
+ up-regulates img/direct-activation.png phosphorylation CD33 0.273
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation FOXP3 0.407
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation IL2RB 0.63
Publications: 5 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling, P38 Signaling, T cell activation
+ down-regulates img/direct_inhibition.png dephosphorylation LCK 0.74
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation LCK 0.598
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation LCK 0.788
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ down-regulates activity img/direct_inhibition.png dephosphorylation LCK 0.74
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKBIA 0.57
Publications: 1
Pathways:T cell activation
+ img/unknown.png phosphorylation LCP2 0.743
Publications: 2 Organism: In Vitro
Pathways:T cell activation
+ up-regulates activity img/direct-activation.png phosphorylation SHC1 0.734
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CD5 0.554
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation LCK 0.788
Publications: 2 Organism: Homo Sapiens, Mus Musculus
Pathways:T cell activation
+ down-regulates img/direct_inhibition.png phosphorylation LCK 0.521
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates img/direct-activation.png phosphorylation ITK 0.537
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation PTPN6 0.598
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.39
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PTPN6 0.598
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SIGLEC10 0.261
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MED28 0.449
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PI3K 0.587
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:T cell activation
+ down-regulates activity img/direct_inhibition.png phosphorylation PIK3R1 0.609
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:T cell activation
+ img/unknown.png phosphorylation SIGLEC10 0.261
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PECAM1 0.572
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation ADAM15 0.356
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PLCG2 0.541
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PRKCQ 0.551
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png dephosphorylation LCK 0.372
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination LCK 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CD247 0.753
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates img/direct-activation.png phosphorylation ERK1/2 0.572
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates img/direct-activation.png binding LCK 0.362
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ up-regulates img/indirect-activation.png MAPK1 0.567
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ up-regulates activity img/direct-activation.png phosphorylation TCR 0.2
Publications: 1 Organism: Mus Musculus
Pathways:T cell activation
+ up-regulates img/direct-activation.png phosphorylation Gbeta 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CD3D 0.551
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png binding LCK 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CD3G 0.54
Publications: 2 Organism: Mus Musculus
Pathways:T cell activation
+ down-regulates img/direct_inhibition.png chemical inhibition LCK 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CD3 0.63
Publications: 1 Organism: Homo Sapiens
Pathways:T cell activation
+ up-regulates activity img/direct-activation.png binding LCK 0.337
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling
+ up-regulates activity img/direct-activation.png phosphorylation DOK1 0.585
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation LCK 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding NOTCH1 0.466
Publications: 1 Organism: Homo Sapiens