LCK - Tyrosine-protein kinase Lck - human protein (Function)
 
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LCK »  Tyrosine-protein kinase Lck   [ EC 2.7.10.2 ]
 
Protein also known as:  Lymphocyte cell-specific protein-tyrosine kinase.
Gene name:  LCK
Entry whose protein(s) existence is based on evidence at protein level
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1 293 3
GENE REF ISO

Function

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Overview 
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.  
8
  • UniProtKB
GO molecular function 
Antigen bindingdefinition[GO:0003823] silver  
1
  • Ortholog Compara
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
ATPase bindingdefinition[GO:0051117]  
1
  • UniProtKB
CD4 receptor bindingdefinition[GO:0042609]  
1
  • UniProtKB
CD8 receptor bindingdefinition[GO:0042610]  
1
  • UniProtKB
Glycoprotein bindingdefinition[GO:0001948]  
4
  • UniProtKB
Identical protein bindingdefinition[GO:0042802]  
1
  • IntAct
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • RefGenome
Phosphatidylinositol 3-kinase bindingdefinition[GO:0043548]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
39
  • IntAct
  • UniProtKB
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • UniProtKB
Protein complex bindingdefinition[GO:0032403] silver  
1
  • Ortholog Compara
Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
Protein phosphatase bindingdefinition[GO:0019903]  
1
  • UniProtKB
Protein serine/threonine phosphatase activitydefinition[GO:0004722]  
2
  • UniProtKB
  • Ortholog Curator
Protein tyrosine kinase activitydefinition[GO:0004713]  
2
  • UniProtKB
  • Ortholog Curator
SH2 domain bindingdefinition[GO:0042169]  
3
  • UniProtKB
  • Ortholog Curator
GO biological process 
Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
2
  • UniProtKB
  • Ortholog Curator
Agingdefinition[GO:0007568] silver  
1
  • Ortholog Compara
B cell receptor signaling pathwaydefinition[GO:0050853]  
1
  • RefGenome
Cellular response to peptide hormone stimulusdefinition[GO:0071375]  
1
  • RefGenome
Cellular zinc ion homeostasisdefinition[GO:0006882]  
2
  • UniProtKB
  • Ortholog Curator
Hemopoiesisdefinition[GO:0030097]  
1
  • UniProtKB
Innate immune responsedefinition[GO:0045087]  
1
  • RefGenome
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Positive regulation of gamma-delta T cell differentiationdefinition[GO:0045588] silver  
1
  • Ortholog Compara
Positive regulation of gene expressiondefinition[GO:0010628] silver  
1
  • Ortholog Compara
Positive regulation of intrinsic apoptotic signaling pathwaydefinition[GO:2001244]  
2
  • UniProtKB
  • Ortholog Curator
Positive regulation of T cell activationdefinition[GO:0050870]  
2
  • UniProtKB
  • Ortholog Curator
Positive regulation of T cell receptor signaling pathwaydefinition[GO:0050862]  
1
  • UniProtKB
Positive regulation of tyrosine phosphorylation of Stat5 proteindefinition[GO:0042523] silver  
1
  • Ortholog Compara
Positive regulation of uterine smooth muscle contractiondefinition[GO:0070474] silver  
1
  • Ortholog Compara
Protein dephosphorylationdefinition[GO:0006470]  
2
  • GOC
  • Ortholog Curator
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • RefGenome
Regulation of lymphocyte activationdefinition[GO:0051249]  
1
  • UniProtKB
Release of sequestered calcium ion into cytosoldefinition[GO:0051209]  
1
  • Ortholog Curator
Response to drugdefinition[GO:0042493]  
2
  • UniProtKB
  • Ortholog Curator
Response to hydrogen peroxidedefinition[GO:0042542] silver  
1
  • Ortholog Compara
Response to mechanical stimulusdefinition[GO:0009612] silver  
1
  • Ortholog Compara
Response to zinc iondefinition[GO:0010043] silver  
1
  • Ortholog Compara
T cell differentiationdefinition[GO:0030217]  
2
  • UniProtKB
  • Ortholog Curator
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • RefGenome
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
2
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
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.  
2
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
HTLV-I infection  hsa05166+3932  
Natural killer cell mediated cytotoxicity  hsa04650+3932  
Osteoclast differentiation  hsa04380+3932  
Primary immunodeficiency  hsa05340+3932  
T cell receptor signaling pathway  hsa04660+3932  
According to Reactome, this protein belongs to the following pathways:
CD28 co-stimulation  R-HSA-389356  
CD28 dependent PI3K/Akt signaling  R-HSA-389357  
CD28 dependent Vav1 pathway  R-HSA-389359  
Constitutive Signaling by Aberrant PI3K in Cancer  R-HSA-2219530  
CTLA4 inhibitory signaling  R-HSA-389513  
DAP12 signaling  R-HSA-2424491  
Downstream TCR signaling  R-HSA-202424  
Generation of second messenger molecules  R-HSA-202433  
GPVI-mediated activation cascade  R-HSA-114604  
Interleukin-2 signaling  R-HSA-451927  
Nef and signal transduction  R-HSA-164944  
Nef Mediated CD4 Down-regulation  R-HSA-167590  
PD-1 signaling  R-HSA-389948  
PECAM1 interactions  R-HSA-210990  
Phosphorylation of CD3 and TCR zeta chains  R-HSA-202427  
PIP3 activates AKT signaling  R-HSA-1257604  
Regulation of KIT signaling  R-HSA-1433559  
Signaling by SCF-KIT  R-HSA-1433557  
Translocation of ZAP-70 to Immunological synapse  R-HSA-202430  
 

Keywords

Biological process 
Host-virus interaction  definition   [KW-0945]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Lck
GenomeRNAi: 3932
PRO: PR:P06239
Chemistry
GuidetoPHARMACOLOGY: 2053