LCK (lymphocyte-specific protein tyrosine kinase)

Identity

Other names	P56-LCK LSK (T cell-specific protein-tyrosine kinase)
	lck tyrosine kinase (AA 1-142)
	membrane associated protein tyrosine kinase
	proto-oncogene LCK
	protein-tyrosine kinase
	put. ptk (135aa); tyrosine kinase
HGNC	LCK
Location	1p34.3
Location_base_pair	Starts at 32512299 and ends at 32524353 bp from pter (hg18-Mar_2006).

DNA/RNA

Description	DNA sequence is located on chromosome no.1 on the arm 1(p).
Transcription	Consists of 13 exons and 12 introns spanning 12.3 kb.
Pseudogene	Unknown

Protein

Description	The kinase p56lck (509 aa) is a T-lymphocyte-specific member of the Src family of non-receptor protein tyrosine kinase. Lck is a 56 kDa phosphoprotein expressed in variety of lymphoid and non-lymphoid cell lineages. Lck contain myristylation sequence, unique amino-terminal regions, followed by Src homology domains SH3 and SH2, a tyrosine kinase catalytic domain, and C-terminal regulatory domain. Lck associates with the inner face of the plasma membrane through its amino-terminus. This interaction is mediated by both myristic acid and palmitic acid that are bound to the amino terminal glycine and Cys-3 and/or Cys-5. The Unique region of Lck represents the domain possessing the greatest sequence diversity within this group of enzymes. This domain is thought to be involved in the interaction of the Lck with specific cellular proteins including Lck substrate. In T-cells it is known, to mediate association with the cytoplasmic tail of T-cell coreceptors CD4 and CD8a. SH3 (Src homology 3) domain is mainly implicated in the regulation of protein-protein interactions, recognizing proline-rich region found in guanine nucleotide exchange factors and GTPase activating proteins. SH2 (Src homology 2) domain of Lck recognizes phosphorylated tyrosine residues on other proteins thereby facilitating the formation of tyrosine phosphorylation-induced multimeric complexes. The tyrosine kinase domain is the catalytic domain of Lck catalyzing the transfer of the gamma-phosphate from ATP to tyrosine residues on proteins. The catalytic domain contains a site of autophosphorylation (Tyr-394), which plays an important role in regulating the protein kinase activity. A C-terminal regulatory domain is also seen containing the major site of tyrosine phosphorylation in vivo (Tyr-505). Phosphorylation of Csk (C-terminal Src kinase) at Tyr-505 leads to inactivation of Lck. Lck is also activated by oxidative stress. Reoxygenation after hypoxia induces Lck kinase activity.
Expression	Expressed in variety of lymphoid and non-lymphoid cell lineages (Breast cancer tissues and other cancers too).
Localisation	Cell membrane
Function	T-cell development, T-cell activation.
Homology	Shares sequence homology with other Src family kinases (Src, Hck, Fyn, Blk, Lyn, Fgr, Yes, and Yrk).

Mutations

Note	Not reported yet

Implicated in

Entity	Breast cancer, T-cell Leukemia, Colon carcinoma.
Oncogenesis	Upregulation of Lck is seen in many cases of Breast cancer. It is also overexpressed in lymphoma, colon cancer. Rearrangement of LCK gene is also reported in murine lymphoma cell line. Oncogenic activation of Lck due translocation of the LCK gene is reported in the human HSB2 T-cell leukemia with t(1;7)(p34;q34) with LCK/ TCRB involvement. Lck regulates cell motility through NF-KB mediated uPA secretion following hypoxia and reoxygenation in Breast cancer.
Disease	Type 1 Diabetes
Prognosis	T-cell mediated Type diabetes (Autoimmune disease) shows defect in TCR/CD3-mediated T-cell activation due to the abnormal expression of LCK.

External links

	Nomenclature
HGNC	LCK   6524
Entrez_Gene	LCK  3932  lymphocyte-specific protein tyrosine kinase
	Cards
Atlas	LCKID14ch1p34
GeneCards	LCK
Ensembl	LCK [Search_View]   ENSG00000182866 [Gene_View]
Genatlas	LCK
GeneLynx	LCK
eGenome	LCK
euGene	3932
	Genomic and cartography
GoldenPath	LCK  -  1p34.3   chr1:32512299-32524353 +  1p34.3   [Description]    (hg18-Mar_2006)
Ensembl	LCK - 1p34.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	LCK
	Gene and transcription
Genbank	AA747421 [ ENTREZ ]
Genbank	AF228313 [ ENTREZ ]
Genbank	AJ865079 [ ENTREZ ]
Genbank	AK098027 [ ENTREZ ]
Genbank	BC013200 [ ENTREZ ]
RefSeq	NM_001042771 [ SRS ]    NM_001042771 [ ENTREZ ]
RefSeq	NM_005356 [ SRS ]    NM_005356 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_032977 [ SRS ]    NT_032977 [ ENTREZ ]
RefSeq	NW_001838577 [ SRS ]    NW_001838577 [ ENTREZ ]
RefSeq	NW_921351 [ SRS ]    NW_921351 [ ENTREZ ]
AceView	LCK AceView - NCBI
Unigene	Hs.470627 [ SRS ]    Hs.470627 [ NCBI ]     HS470627 [ spliceNest ]
Fast-db	12917 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P06239 [ SRS]    P06239 [ EXPASY ]     P06239 [ INTERPRO ]     P06239 [ UNIPROT ]
Prosite	PS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
Prosite	PS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
Prosite	PS00109 PROTEIN_KINASE_TYR [ SRS ]    PS00109 PROTEIN_KINASE_TYR [ Expasy ]
Prosite	PS50001 SH2 [ SRS ]    PS50001 SH2 [ Expasy ]
Prosite	PS50002 SH3 [ SRS ]    PS50002 SH3 [ Expasy ]
Interpro	IPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
Interpro	IPR017441 Protein_kinase_ATP_bd_CS [ SRS ]    IPR017441 Protein_kinase_ATP_bd_CS [ EBI ]
Interpro	IPR000980 SH2 [ SRS ]    IPR000980 SH2 [ EBI ]
Interpro	IPR001452 SH3 [ SRS ]    IPR001452 SH3 [ EBI ]
Interpro	IPR001245 Tyr_pkinase [ SRS ]    IPR001245 Tyr_pkinase [ EBI ]
Interpro	IPR008266 Tyr_pkinase_AS [ SRS ]    IPR008266 Tyr_pkinase_AS [ EBI ]
CluSTr	P06239
Pfam	PF07714 Pkinase_Tyr [ SRS ]    PF07714 Pkinase_Tyr [ Sanger ]    pfam07714 [ NCBI-CDD ]
Pfam	PF00017 SH2 [ SRS ]    PF00017 SH2 [ Sanger ]    pfam00017 [ NCBI-CDD ]
Pfam	PF00018 SH3_1 [ SRS ]    PF00018 SH3_1 [ Sanger ]    pfam00018 [ NCBI-CDD ]
Smart	SM00252 SH2 [EMBL]
Smart	SM00326 SH3 [EMBL]
Smart	SM00219 TyrKc [EMBL]
Prodom	PD000001 Prot_kinase[INRA-Toulouse]
Prodom	P06239 LCK_HUMAN [ Domain structure ]   P06239 LCK_HUMAN  [ sequences sharing at least 1 domain ]
Prodom	PD000001[INRA-Toulouse]
Prodom	P06239 LCK_HUMAN [ Domain structure ]   P06239 LCK_HUMAN  [ sequences sharing at least 1 domain ]
Prodom	PD000001[INRA-Toulouse]
Prodom	P06239 LCK_HUMAN [ Domain structure ]   P06239 LCK_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P06239
PDB	1BHF [ SRS ]    1BHF [ PdbSum ],   1BHF [ IMB ]   1BHF [ RSDB ]
PDB	1BHH [ SRS ]    1BHH [ PdbSum ],   1BHH [ IMB ]   1BHH [ RSDB ]
PDB	1CWD [ SRS ]    1CWD [ PdbSum ],   1CWD [ IMB ]   1CWD [ RSDB ]
PDB	1CWE [ SRS ]    1CWE [ PdbSum ],   1CWE [ IMB ]   1CWE [ RSDB ]
PDB	1FBZ [ SRS ]    1FBZ [ PdbSum ],   1FBZ [ IMB ]   1FBZ [ RSDB ]
PDB	1H92 [ SRS ]    1H92 [ PdbSum ],   1H92 [ IMB ]   1H92 [ RSDB ]
PDB	1IJR [ SRS ]    1IJR [ PdbSum ],   1IJR [ IMB ]   1IJR [ RSDB ]
PDB	1KIK [ SRS ]    1KIK [ PdbSum ],   1KIK [ IMB ]   1KIK [ RSDB ]
PDB	1LCJ [ SRS ]    1LCJ [ PdbSum ],   1LCJ [ IMB ]   1LCJ [ RSDB ]
PDB	1LCK [ SRS ]    1LCK [ PdbSum ],   1LCK [ IMB ]   1LCK [ RSDB ]
PDB	1LKK [ SRS ]    1LKK [ PdbSum ],   1LKK [ IMB ]   1LKK [ RSDB ]
PDB	1LKL [ SRS ]    1LKL [ PdbSum ],   1LKL [ IMB ]   1LKL [ RSDB ]
PDB	1Q68 [ SRS ]    1Q68 [ PdbSum ],   1Q68 [ IMB ]   1Q68 [ RSDB ]
PDB	1Q69 [ SRS ]    1Q69 [ PdbSum ],   1Q69 [ IMB ]   1Q69 [ RSDB ]
PDB	1QPC [ SRS ]    1QPC [ PdbSum ],   1QPC [ IMB ]   1QPC [ RSDB ]
PDB	1QPD [ SRS ]    1QPD [ PdbSum ],   1QPD [ IMB ]   1QPD [ RSDB ]
PDB	1QPE [ SRS ]    1QPE [ PdbSum ],   1QPE [ IMB ]   1QPE [ RSDB ]
PDB	1QPJ [ SRS ]    1QPJ [ PdbSum ],   1QPJ [ IMB ]   1QPJ [ RSDB ]
PDB	1X27 [ SRS ]    1X27 [ PdbSum ],   1X27 [ IMB ]   1X27 [ RSDB ]
PDB	2IIM [ SRS ]    2IIM [ PdbSum ],   2IIM [ IMB ]   2IIM [ RSDB ]
PDB	2OF2 [ SRS ]    2OF2 [ PdbSum ],   2OF2 [ IMB ]   2OF2 [ RSDB ]
PDB	2OF4 [ SRS ]    2OF4 [ PdbSum ],   2OF4 [ IMB ]   2OF4 [ RSDB ]
PDB	2OFU [ SRS ]    2OFU [ PdbSum ],   2OFU [ IMB ]   2OFU [ RSDB ]
PDB	2OFV [ SRS ]    2OFV [ PdbSum ],   2OFV [ IMB ]   2OFV [ RSDB ]
PDB	2OG8 [ SRS ]    2OG8 [ PdbSum ],   2OG8 [ IMB ]   2OG8 [ RSDB ]
PDB	2PL0 [ SRS ]    2PL0 [ PdbSum ],   2PL0 [ IMB ]   2PL0 [ RSDB ]
PDB	3B2W [ SRS ]    3B2W [ PdbSum ],   3B2W [ IMB ]   3B2W [ RSDB ]
PDB	3LCK [ SRS ]    3LCK [ PdbSum ],   3LCK [ IMB ]   3LCK [ RSDB ]
HPRD	01080
	Protein Interaction databases
DIP	P06239
IntAct	P06239
	Polymorphism : SNP, mutations, diseases
OMIM	153390    [ map ]
GENECLINICS	153390
SNP	LCK [dbSNP-NCBI]
SNP	NM_001042771 [SNP-NCI]
SNP	NM_005356 [SNP-NCI]
SNP	LCK [GeneSNPs - Utah]  LCK] [HGBASE - SRS]
HAPMAP	LCK [HAPMAP]
COSMIC	LCK [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	LCK [Translocation breakpoints In Cancer]
HGMD	LCK
	General knowledge
Family Browser	LCK [UCSC Family Browser]
SOURCE	NM_001042771
SOURCE	NM_005356
SMD	Hs.470627
SAGE	Hs.470627
Enzyme	2.7.10.2 [ Enzyme-Expasy ]   2.7.10.2 [ Enzyme-SRS ]   2.7.10.2 [ IntEnz-EBI ]   2.7.10.2 [ BRENDA ]   2.7.10.2 [ KEGG ]   2.7.10.2 [ WIT ]
GO	nucleotide binding [Amigo]  nucleotide binding
GO	pericentriolar material [Amigo]  pericentriolar material
GO	glycoprotein binding [Amigo]  glycoprotein binding
GO	protein tyrosine kinase activity [Amigo]  protein tyrosine kinase activity
GO	non-membrane spanning protein tyrosine kinase activity [Amigo]  non-membrane spanning protein tyrosine kinase activity
GO	protein serine/threonine phosphatase activity [Amigo]  protein serine/threonine phosphatase activity
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	plasma membrane [Amigo]  plasma membrane
GO	plasma membrane [Amigo]  plasma membrane
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	cellular zinc ion homeostasis [Amigo]  cellular zinc ion homeostasis
GO	induction of apoptosis [Amigo]  induction of apoptosis
GO	caspase activation [Amigo]  caspase activation
GO	intracellular signaling cascade [Amigo]  intracellular signaling cascade
GO	Ras protein signal transduction [Amigo]  Ras protein signal transduction
GO	protein C-terminus binding [Amigo]  protein C-terminus binding
GO	transferase activity [Amigo]  transferase activity
GO	protein kinase binding [Amigo]  protein kinase binding
GO	hemopoiesis [Amigo]  hemopoiesis
GO	T cell differentiation [Amigo]  T cell differentiation
GO	SH2 domain binding [Amigo]  SH2 domain binding
GO	response to drug [Amigo]  response to drug
GO	CD4 receptor binding [Amigo]  CD4 receptor binding
GO	CD8 receptor binding [Amigo]  CD8 receptor binding
GO	phosphoinositide 3-kinase binding [Amigo]  phosphoinositide 3-kinase binding
GO	interspecies interaction between organisms [Amigo]  interspecies interaction between organisms
GO	membrane raft [Amigo]  membrane raft
GO	positive regulation of T cell receptor signaling pathway [Amigo]  positive regulation of T cell receptor signaling pathway
GO	positive regulation of T cell activation [Amigo]  positive regulation of T cell activation
GO	ATPase binding [Amigo]  ATPase binding
GO	release of sequestered calcium ion into cytosol [Amigo]  release of sequestered calcium ion into cytosol
GO	regulation of lymphocyte activation [Amigo]  regulation of lymphocyte activation
BIOCARTA	Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor    [Genes]
BIOCARTA	The Co-Stimulatory Signal During T-cell Activation    [Genes]
BIOCARTA	IL 2 signaling pathway    [Genes]
BIOCARTA	IL-7 Signal Transduction    [Genes]
BIOCARTA	T Cell Receptor Signaling Pathway    [Genes]
BIOCARTA	Lck and Fyn tyrosine kinases in initiation of TCR Activation    [Genes]
KEGG	Natural killer cell mediated cytotoxicity
KEGG	T cell receptor signaling pathway
PubGene	LCK
TreeFam	LCK
CTD	3932 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	LCK Related clones (RZPD - Berlin)
	PubMed
PubMed	299 Pubmed reference(s) in Entrez

Bibliography

Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells.

Foss FM, Veillette A, Sartor O, Rosen N, Bolen JB

Oncogene research. 1989 ; 5 (1) : 13-23.

PMID 2476706

lck suppresses gene expression from various promoters including human T-cell leukemia virus type I promoter.

Ohta M, Morita T, Shimotohno K

Japanese journal of cancer research : Gann. 1990 ; 81 (5) : 440-444.

PMID 2116390

Activation of the Lck tyrosine protein kinase by hydrogen peroxide requires the phosphorylation of Tyr-394.

Hardwick JS, Sefton BM

Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (10) : 4527-4531.

PMID 7538674

Specific deficiency of p56lck expression in T lymphocytes from type 1 diabetic patients.

Nervi S, Atlan-Gepner C, Kahn-Perles B, Lecine P, Vialettes B, Imbert J, Naquet P

Journal of immunology (Baltimore, Md. : 1950). 2000 ; 165 (10) : 5874-5883.

PMID 11067948

Tyrosine kinase p56lck regulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through tyrosine phosphorylation of IkappaBalpha following hypoxia/reoxygenation.

Mahabeleshwar GH, Kundu GC

The Journal of biological chemistry. 2003 ; 278 (52) : 52598-52612.

PMID 14534291

Tyrosine kinase, p56lck-induced cell motility, and urokinase-type plasminogen activator secretion involve activation of epidermal growth factor receptor/extracellular signal regulated kinase pathways.

Mahabeleshwar GH, Das R, Kundu GC

The Journal of biological chemistry. 2004 ; 279 (11) : 9733-9742.

PMID 14699120

Structure and regulation of Src family kinases.

Boggon TJ, Eck MJ

Oncogene. 2004 ; 23 (48) : 7918-7927.

PMID 15489910

Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.

Palacios EH, Weiss A

Oncogene. 2004 ; 23 (48) : 7990-8000.

PMID 15489916

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	05-2005	Deepak Pralhad Patil, Gopal Chandra Kundu
		CSIR-JRF,c/o Dr. G. C. Kundu, National Center for Cell Science, NCCS Complex, Ganeshkhind, Pune(Maharastra)-411007, India

Citation

This paper should be referenced as such :

Patil DP, Kundu GC . LCK (lymphocyte-specific protein tyrosine kinase). Atlas Genet Cytogenet Oncol Haematol. May 2005 . URL : http://AtlasGeneticsOncology.org/Genes/LCKID14ch1p34.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Oct 11 12:53:03 2008