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Tyrosine-protein kinase CSK

From Wikipedia, the free encyclopedia
Kinase enzyme that phosphorylates Src-family kinases
This article is about the kinase CSK, for the kinase that is phosphorylated by CSK, seec-Src.
CSK
Available structures
PDBOrtholog search:H3BU69 PDBeH3BU69 RCSB
List of PDB id codes

1BYG,1CSK,3D7T,3D7U,3EAC,3EAZ

Identifiers
AliasesCSK, Src, c-src tyrosine kinase, CSK/Src, non-receptor tyrosine kinase, C-terminal Src kinase
External IDsOMIM:190090,124095;MGI:88537;HomoloGene:55818;GeneCards:CSK;OMA:CSK - orthologs
Gene location (Human)
Chromosome 15 (human)
Chr.Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for CSK
Genomic location for CSK
Band15q24.1Start74,782,057bp[1]
End74,803,198bp[1]
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)[2]
Chromosome 9 (mouse)
Genomic location for CSK
Genomic location for CSK
Band9 B|9 31.18 cMStart57,533,929bp[2]
End57,560,914bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • granulocyte

  • monocyte

  • spleen

  • blood

  • lymph node

  • appendix

  • mucosa of transverse colon

  • tonsil

  • bone marrow cells

  • stromal cell of endometrium
Top expressed in
  • granulocyte

  • mesenteric lymph nodes

  • thymus

  • spleen

  • neural layer of retina

  • lip

  • ventricular zone

  • blood

  • yolk sac

  • gastrula
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
Entrez

1445

12988

Ensembl

ENSG00000103653

ENSMUSG00000032312

UniProt

P41240

P41241

RefSeq (mRNA)

NM_001127190
NM_004383
NM_001354988

NM_007783
NM_001304761

RefSeq (protein)

NP_001120662
NP_004374
NP_001341917

NP_001291690
NP_031809

Location (UCSC)Chr 15: 74.78 – 74.8 MbChr 9: 57.53 – 57.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tyrosine-protein kinase CSK also known asC-terminal Src kinase is anenzyme that, in humans, is encoded by the CSKgene.[5] This enzyme phosphorylatestyrosine residues located in theC-terminal end ofSrc-family kinases (SFKs) includingSRC,HCK,FYN,LCK,LYN andYES1.[6][7]

Function

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This Non-receptor tyrosine-protein kinase plays an important role in the regulation ofcell growth, differentiation,migration andimmune response. CSK acts by suppressing the activity of theSrc family of protein kinases byphosphorylation of Src family members at a conserved C-terminal tail site in Src.[8][9][10][11] Upon phosphorylation by otherkinases, Src-family members engage inintramolecular interactions between thephosphotyrosine tail and theSH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is then recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane and ultimately suppresses signaling through various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several effector molecules.[6][7]

Role in development and regulation

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Tyrosine-protein kinase CSK is involved in the following developmental, metabolic, andsignal transduction cascades:

Adherens junction organization, blood coagulation, brain development, cell differentiation, cell migration, cellular response to peptide hormone stimulus, central nervous system development, epidermal growth factor receptor signaling pathway, innate immune response, epitheliummorphogenesis, regulation ofbone resorption, negative regulation of cell proliferation, negative regulation ofERK1 andERK2 cascade, negative regulation ofGolgi to plasma membrane protein transport, negative regulation ofinterleukin-6 production, negative regulation of kinase activity, negative regulation oflow-density lipoprotein particle clearance, negative regulation ofphagocytosis, dendrocyte differentiation, peptidyl-tyrosine autophosphorylation, platelet activation, positive regulation ofMAP kinase activity, regulation of cell proliferation, regulation ofcytokine production, regulation ofFc receptor mediated stimulatory signaling pathway,T cell costimulation,T cell receptor signaling pathway.[12]

Expression and subcellular location

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CSK is expressed in the lungs and macrophages as well as several other tissues.[13] Tyrosine-Kinase CSK is mainly present in the cytoplasm, but also found in lipid rafts making cell-cell junction.[12]

Mutations

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Clinical significance

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Csk's interaction with a phosphatase ("Lyp", gene product ofPTPN22) is possibly associated with the increasedautoimmune diseases associated withPTPN22 mutations.[16]

References

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  1. ^abcGRCh38: Ensembl release 89: ENSG00000103653Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000032312Ensembl, May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^"Entrez Gene: C-src tyrosine kinase". Retrieved2013-07-11.
  6. ^abBergman M, Mustelin T, Oetken C, Partanen J, Flint NA, Amrein KE, Autero M, Burn P, Alitalo K (Aug 1992)."The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity".The EMBO Journal.11 (8):2919–24.doi:10.1002/j.1460-2075.1992.tb05361.x.PMC 556773.PMID 1639064.
  7. ^abSun G, Budde RJ (Sep 1997). "Expression, purification, and initial characterization of human Yes protein tyrosine kinase from a bacterial expression system".Archives of Biochemistry and Biophysics.345 (1):135–42.doi:10.1006/abbi.1997.0236.PMID 9281320.
  8. ^Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src".Nature.351 (6321):69–72.Bibcode:1991Natur.351...69N.doi:10.1038/351069a0.PMID 1709258.S2CID 4363527.
  9. ^Nada S, Yagi T, Takeda H, Tokunaga T, Nakagawa H, Ikawa Y, Okada M, Aizawa S (Jun 1993). "Constitutive activation of Src family kinases in mouse embryos that lack Csk".Cell.73 (6):1125–35.doi:10.1016/0092-8674(93)90642-4.PMID 8513497.S2CID 37988394.
  10. ^Chong YP, Chan AS, Chan KC, Williamson NA, Lerner EC, Smithgall TE, Bjorge JD, Fujita DJ, Purcell AW, Scholz G, Mulhern TD, Cheng HC (Nov 2006)."C-terminal Src kinase-homologous kinase (CHK), a unique inhibitor inactivating multiple active conformations of Src family tyrosine kinases".The Journal of Biological Chemistry.281 (44):32988–99.doi:10.1074/jbc.M602951200.PMC 4281726.PMID 16959780.
  11. ^Chong YP, Mulhern TD, Cheng HC (Sep 2005). "C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK)--endogenous negative regulators of Src-family protein kinases".Growth Factors.23 (3):233–44.doi:10.1080/08977190500178877.PMID 16243715.S2CID 38227036.
  12. ^abUniversal protein resource accession numberP41240 for "Tyrosine-protein kinase CSK" atUniProt.
  13. ^Bräuninger A, Holtrich U, Strebhardt K, Rübsamen-Waigmann H (Jan 1992). "Isolation and characterization of a human gene that encodes a new subclass of protein tyrosine kinases".Gene.110 (2):205–11.doi:10.1016/0378-1119(92)90649-a.PMID 1371489.
  14. ^abJoukov V, Vihinen M, Vainikka S, Sowadski JM, Alitalo K, Bergman M (Mar 1997)."Identification of csk tyrosine phosphorylation sites and a tyrosine residue important for kinase domain structure".The Biochemical Journal.322 (3):927–35.doi:10.1042/bj3220927.PMC 1218276.PMID 9148770.
  15. ^Vang T, Torgersen KM, Sundvold V, Saxena M, Levy FO, Skålhegg BS, Hansson V, Mustelin T, Taskén K (Feb 2001)."Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor".The Journal of Experimental Medicine.193 (4):497–507.doi:10.1084/jem.193.4.497.PMC 2195911.PMID 11181701.
  16. ^Fiorillo E, Orrú V, Stanford SM, Liu Y, Salek M, Rapini N, Schenone AD, Saccucci P, Delogu LG, Angelini F, Manca Bitti ML, Schmedt C, Chan AC, Acuto O, Bottini N (Aug 2010)."Autoimmune-associated PTPN22 R620W variation reduces phosphorylation of lymphoid phosphatase on an inhibitory tyrosine residue".The Journal of Biological Chemistry.285 (34):26506–18.doi:10.1074/jbc.M110.111104.PMC 2924087.PMID 20538612.

External links

[edit]
Growth factor receptors
EGF receptor family
Insulin receptor family
PDGF receptor family
FGF receptor family
VEGF receptors family
HGF receptor family
Trk receptor family
EPH receptor family
LTK receptor family
TIE receptor family
ROR receptor family
DDR receptor family
PTK7 receptor family
RYK receptor family
MuSK receptor family
ROS receptor family
AATYK receptor family
AXL receptor family
RET receptor family
uncategorised
ABL family
ACK family
CSK family
FAK family
FES family
FRK family
JAK family
SRC-A family
SRC-B family
TEC family
SYK family
Activity
Regulation
Classification
Kinetics
Types
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