Names & Taxonomy

Uniprot ID:
P06239
Entry Name:
LCK_HUMAN
Status:
reviewed
Protein Names:
Tyrosine-protein kinase Lck (EC 2.7.10.2) (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)
Gene Names:
LCK
Gene Names Primary:
LCK
Organism:
Homo sapiens (Human)

Structure

Length:
509
Sequence:
MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKERPEDRPTFDYLRSVLEDFFTATEGQYQPQP
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 364 364 Proton acceptor.
Cross Reference Drug Bank:
DB01254 DB09079 DB08901
Gene Ontology Go:
cytosol
extracellular exosome
extrinsic component of cytoplasmic side of plasma membrane
immunological synapse
membrane raft
pericentriolar material
plasma membrane
ATP binding
ATPase binding
CD4 receptor binding
CD8 receptor binding
glycoprotein binding
identical protein binding
non-membrane spanning protein tyrosine kinase activity
phosphatidylinositol 3-kinase binding
protein C-terminus binding
protein kinase binding
protein phosphatase binding
protein serine/threonine phosphatase activity
protein tyrosine kinase activity
SH2 domain binding
activation of cysteine-type endopeptidase activity involved in apoptotic process
B cell receptor signaling pathway
blood coagulation
cellular zinc ion homeostasis
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
hemopoiesis
innate immune response
leukocyte migration
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
phosphatidylinositol-mediated signaling
platelet activation
positive regulation of intrinsic apoptotic signaling pathway
positive regulation of T cell activation
positive regulation of T cell receptor signaling pathway
protein dephosphorylation
protein phosphorylation
regulation of cell proliferation
regulation of defense response to virus by virus
regulation of lymphocyte activation
release of sequestered calcium ion into cytosol
response to drug
T cell costimulation
T cell differentiation
T cell receptor signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
viral process
Gene Ontology Biological Process:
activation of cysteine-type endopeptidase activity involved in apoptotic process
B cell receptor signaling pathway
blood coagulation
cellular zinc ion homeostasis
epidermal growth factor receptor signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
hemopoiesis
innate immune response
leukocyte migration
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
phosphatidylinositol-mediated signaling
platelet activation
positive regulation of intrinsic apoptotic signaling pathway
positive regulation of T cell activation
positive regulation of T cell receptor signaling pathway
protein dephosphorylation
protein phosphorylation
regulation of cell proliferation
regulation of defense response to virus by virus
regulation of lymphocyte activation
release of sequestered calcium ion into cytosol
response to drug
T cell costimulation
T cell differentiation
T cell receptor signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
viral process
Gene Ontology Molecular Function:
ATPase binding
ATP binding
CD4 receptor binding
CD8 receptor binding
glycoprotein binding
identical protein binding
non-membrane spanning protein tyrosine kinase activity
phosphatidylinositol 3-kinase binding
protein C-terminus binding
protein kinase binding
protein phosphatase binding
protein serine/threonine phosphatase activity
protein tyrosine kinase activity
SH2 domain binding
Gene Ontology Cellular Component:
cytosol
extracellular exosome
extrinsic component of cytoplasmic side of plasma membrane
immunological synapse
membrane raft
pericentriolar material
plasma membrane
Keywords:
3D-structure
ATP-binding
Alternative splicing
Cell membrane
Chromosomal rearrangement
Complete proteome
Cytoplasm
Disease mutation
Host-virus interaction
Kinase
Lipoprotein
Membrane
Myristate
Nucleotide-binding
Palmitate
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
SH2 domain
SH3 domain
Transferase
Tyrosine-protein kinase
Interacts With:
Itself; P22575; Q9YJQ8; Q13444; P10275; P20749; P01730; Q5VV42; Q13480; P08238; Q07666; P10721; O43561; Q9BRK4; Q9H204; P08581; P04150; Q04759; Q9Y2R2; P29350; P08575; Q9NP31; P43405; P0CG48; P43403

Publication

PubMed ID:
3493153 3265417 2558056 8139546 7495859 12401726 16710414 15489334 2850479 2787474 11009097 2835736 3489486 1639064 7504174 7852312 8618896 8631775 8794306 9178760 10848956 12218089 11840567 14610046 14610044 12837766 14757743 16339550 15592455 16461343 16709819 17634955 18691976 19369195 19690332 20100835 20028775 20851766 22080863 21269457 21917715 21406692 23946459 7512222 7532720 8604142 8945479 9685372 22985903