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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1 237 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.  
7
  • CuratedUniProtKB
GO molecular function 
Antigen bindingdefinition[GO:0003823] silver  
  • IEAOrtholog Compara
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
ATPase bindingdefinition[GO:0051117]  
1
  • IPIUniProtKB
CD4 receptor bindingdefinition[GO:0042609]  
1
  • IPIUniProtKB
CD8 receptor bindingdefinition[GO:0042610]  
1
  • IPIUniProtKB
Glycoprotein bindingdefinition[GO:0001948]  
4
  • IPIUniProtKB
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
  • IEAEC 2 GO
Phosphatidylinositol 3-kinase bindingdefinition[GO:0043548]  
1
  • IPIUniProtKB
Protein bindingdefinition[GO:0005515]  
36
  • IPIIntAct
  • IPIUniProtKB
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • IPIUniProtKB
Protein complex bindingdefinition[GO:0032403] silver  
  • IEAOrtholog Compara
Protein kinase bindingdefinition[GO:0019901]  
1
  • IPIUniProtKB
Protein phosphatase bindingdefinition[GO:0019903]  
1
  • IPIUniProtKB
Protein serine/threonine phosphatase activitydefinition[GO:0004722]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
SH2 domain bindingdefinition[GO:0042169]  
2
  • IPIUniProtKB
  • ISSOrtholog Curator
GO biological process 
Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Agingdefinition[GO:0007568] silver  
  • IEAOrtholog Compara
B cell receptor signaling pathwaydefinition[GO:0050853] silver  
  • IEAOrtholog Compara
Cellular zinc ion homeostasisdefinition[GO:0006882]  
1
  • IEPUniProtKB
  • ISSOrtholog Curator
Dephosphorylationdefinition[GO:0016311]  
1
  • IDAGOC
  • ISSOrtholog Curator
Hemopoiesisdefinition[GO:0030097]  
1
  • NASUniProtKB
Positive regulation of gamma-delta T cell differentiationdefinition[GO:0045588] silver  
  • IEAOrtholog Compara
Positive regulation of gene expressiondefinition[GO:0010628] silver  
  • IEAOrtholog Compara
Positive regulation of intrinsic apoptotic signaling pathwaydefinition[GO:2001244]  
1
  • IMPUniProtKB
  • ISSOrtholog Curator
Positive regulation of T cell activationdefinition[GO:0050870]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Positive regulation of T cell receptor signaling pathwaydefinition[GO:0050862]  
1
  • NASUniProtKB
Positive regulation of tyrosine phosphorylation of Stat5 proteindefinition[GO:0042523] silver  
  • IEAOrtholog Compara
Positive regulation of uterine smooth muscle contractiondefinition[GO:0070474] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of lymphocyte activationdefinition[GO:0051249]  
1
  • NASUniProtKB
Release of sequestered calcium ion into cytosoldefinition[GO:0051209]  
  • ISSOrtholog Curator
Response to drugdefinition[GO:0042493]  
1
  • IDAUniProtKB
  • ISSOrtholog Curator
Response to hydrogen peroxidedefinition[GO:0042542] silver  
  • IEAOrtholog Compara
Response to mechanical stimulusdefinition[GO:0009612] silver  
  • IEAOrtholog Compara
Response to zinc iondefinition[GO:0010043] silver  
  • IEAOrtholog Compara
T cell differentiationdefinition[GO:0030217]  
1
  • IMPUniProtKB
  • ISSOrtholog Curator
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.  
  • CuratedUniProtKB
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.  
1
  • CuratedUniProtKB
 
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:
Disease  REACT_116125  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

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