InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LCK

Summary

InnateDB Protein

IDBP-95673.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LCK

Protein Name

lymphocyte-specific protein tyrosine kinase

Synonyms

IMD22; LSK; p56lck; pp58lck; YT16;

Species

Homo sapiens

Ensembl Protein

ENSP00000337825

InnateDB Gene

IDBG-95667 (LCK)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:16339550, ECO:0000269PubMed:16709819, ECO:0000269PubMed:20028775, ECO:0000269PubMed:20100835, ECO:0000269PubMed:20851766, ECO:0000269PubMed:21269457, ECO:0000269PubMed:22080863}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:12218089}. Cell membrane {ECO:0000269PubMed:12218089}; Lipid-anchor {ECO:0000269PubMed:12218089}; Cytoplasmic side {ECO:0000269PubMed:12218089}. Note=Present in lipid rafts in an inactive form.

Disease Associations

Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.

Tissue Specificity

Expressed specifically in lymphoid cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 168 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	168 [view]
Protein-Protein	168 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001948	glycoprotein binding
GO:0003823	antigen binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0004722	protein serine/threonine phosphatase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0019903	protein phosphatase binding
GO:0032403	protein complex binding
GO:0042169	SH2 domain binding
GO:0042609	CD4 receptor binding
GO:0042610	CD8 receptor binding
GO:0042802	identical protein binding
GO:0043548	phosphatidylinositol 3-kinase binding
GO:0051117	ATPase binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006882	cellular zinc ion homeostasis
GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007166	cell surface receptor signaling pathway
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007568	aging
GO:0007596	blood coagulation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009612	response to mechanical stimulus
GO:0010038	response to metal ion
GO:0010043	response to zinc ion
GO:0010628	positive regulation of gene expression
GO:0016032	viral process
GO:0016311	dephosphorylation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030097	hemopoiesis
GO:0030168	platelet activation
GO:0030217	T cell differentiation
GO:0031295	T cell costimulation
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042493	response to drug
GO:0042523	positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0042542	response to hydrogen peroxide
GO:0045087	innate immune response
GO:0045588	positive regulation of gamma-delta T cell differentiation
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0050690	regulation of defense response to virus by virus
GO:0050852	T cell receptor signaling pathway
GO:0050853	B cell receptor signaling pathway
GO:0050856	regulation of T cell receptor signaling pathway
GO:0050862	positive regulation of T cell receptor signaling pathway
GO:0050870	positive regulation of T cell activation
GO:0050900	leukocyte migration
GO:0051209	release of sequestered calcium ion into cytosol
GO:0051249	regulation of lymphocyte activation
GO:0070474	positive regulation of uterine smooth muscle contraction
GO:2001244	positive regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0000242	pericentriolar material
GO:0001772	immunological synapse
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0030139	endocytic vesicle
GO:0045121	membrane raft
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM