This Non-receptor tyrosine-protein kinase plays an important role in the regulation of cell growth, differentiation, migration and immune response. CSK acts by suppressing the activity of the Src family of protein kinases by phosphorylation of Src family members at a conserved C-terminal tail site in Src.[8][9][10][11] Upon phosphorylation by other kinases, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 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
Tyrosine-protein kinase CSK is involved in the following developmental, metabolic, and signal 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, epithelium morphogenesis, regulation of bone resorption, negative regulation of cell proliferation, negative regulation of ERK1 and ERK2 cascade, negative regulation of Golgi to plasma membrane protein transport, negative regulation of interleukin-6 production, negative regulation of kinase activity, negative regulation of low-density lipoprotein particle clearance, negative regulation of phagocytosis, dendrocyte differentiation, peptidyl-tyrosine autophosphorylation, platelet activation, positive regulation of MAP kinase activity, regulation of cell proliferation, regulation of cytokine production, regulation of Fc receptor mediated stimulatory signaling pathway, T cell costimulation, T cell receptor signaling pathway.[12]
Expression and subcellular location
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]
Csk's interaction with a phosphatase ("Lyp", gene product of PTPN22) is possibly associated with the increased autoimmune diseases associated with PTPN22 mutations.[16]
References
^ abcGRCh38: Ensembl release 89: ENSG00000103653 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000032312 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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. PMC556773. PMID 1639064.
^ 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.
^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.
^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.
^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. PMC4281726. PMID 16959780.
^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.
^ abUniversal protein resource accession number P41240 for "Tyrosine-protein kinase CSK" at UniProt.
^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.
^ 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. PMC1218276. PMID 9148770.
^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. PMC2195911. PMID 11181701.
^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. PMC2924087. PMID 20538612.
External links
CSK tyrosine-protein kinase at the US National Library of Medicine Medical Subject Headings (MeSH)
tyrosine, protein, kinase, this, article, about, kinase, kinase, that, phosphorylated, also, known, terminal, kinase, enzyme, that, humans, encoded, gene, this, enzyme, phosphorylates, tyrosine, residues, located, terminal, family, kinases, sfks, including, ye. This article is about the kinase CSK for the kinase that is phosphorylated by CSK see c Src Tyrosine protein kinase CSK also known as C terminal Src kinase is an enzyme that in humans is encoded by the CSK gene 5 This enzyme phosphorylates tyrosine residues located in the C terminal end of Src family kinases SFKs including SRC HCK FYN LCK LYN and YES1 6 7 CSKAvailable structuresPDBOrtholog search H3BU69 PDBe H3BU69 RCSBList of PDB id codes1BYG 1CSK 3D7T 3D7U 3EAC 3EAZIdentifiersAliasesCSK Src c src tyrosine kinase CSK Src non receptor tyrosine kinase C terminal Src kinaseExternal IDsOMIM 190090 124095 MGI 88537 HomoloGene 55818 GeneCards CSKGene location Human Chr Chromosome 15 human 1 Band15q24 1Start74 782 057 bp 1 End74 803 198 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 B 9 31 18 cMStart57 533 929 bp 2 End57 560 914 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytespleenbloodlymph nodeappendixthymusbone marrow cellsstromal cell of endometriumpancreatic ductal cellright lobe of liverTop expressed inthymusspleenlipbloodyolk sacesophagusankle jointganglionic eminencebone marrowduodenumMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontransferase activity nucleotide binding protein kinase activity protein kinase A catalytic subunit binding non membrane spanning protein tyrosine kinase activity metal ion binding protein C terminus binding protein binding identical protein binding protein tyrosine kinase activity protein phosphatase binding proline rich region binding signaling receptor binding ATP binding kinase activityCellular componentcytoplasm cytosol membrane cell cell junction extrinsic component of cytoplasmic side of plasma membrane plasma membrane membrane raft extracellular exosomeBiological processcell differentiation adaptive immune response positive regulation of MAP kinase activity epidermal growth factor receptor signaling pathway negative regulation of phagocytosis phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway negative regulation of low density lipoprotein particle clearance immune system process negative regulation of interleukin 6 production T cell costimulation oligodendrocyte differentiation negative regulation of Golgi to plasma membrane protein transport regulation of Fc receptor mediated stimulatory signaling pathway regulation of cytokine production protein phosphorylation brain development cellular response to peptide hormone stimulus regulation of cell population proliferation peptidyl tyrosine autophosphorylation negative regulation of ERK1 and ERK2 cascade protein autophosphorylation innate immune response adherens junction organization T cell receptor signaling pathway negative regulation of cell population proliferation negative regulation of bone resorption negative regulation of kinase activity central nervous system development peptidyl tyrosine phosphorylationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez144512988EnsemblENSG00000103653ENSMUSG00000032312UniProtP41240P41241RefSeq mRNA NM 001127190NM 004383NM 001354988NM 007783NM 001304761RefSeq protein NP 001120662NP 004374NP 001341917NP 001291690NP 031809Location UCSC Chr 15 74 78 74 8 MbChr 9 57 53 57 56 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Role in development and regulation 3 Expression and subcellular location 4 Mutations 5 Clinical significance 6 References 7 External linksFunction EditThis Non receptor tyrosine protein kinase plays an important role in the regulation of cell growth differentiation migration and immune response CSK acts by suppressing the activity of the Src family of protein kinases by phosphorylation of Src family members at a conserved C terminal tail site in Src 8 9 10 11 Upon phosphorylation by other kinases Src family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 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 EditTyrosine protein kinase CSK is involved in the following developmental metabolic and signal 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 epithelium morphogenesis regulation of bone resorption negative regulation of cell proliferation negative regulation of ERK1 and ERK2 cascade negative regulation of Golgi to plasma membrane protein transport negative regulation of interleukin 6 production negative regulation of kinase activity negative regulation of low density lipoprotein particle clearance negative regulation of phagocytosis dendrocyte differentiation peptidyl tyrosine autophosphorylation platelet activation positive regulation of MAP kinase activity regulation of cell proliferation regulation of cytokine production regulation of Fc receptor mediated stimulatory signaling pathway T cell costimulation T cell receptor signaling pathway 12 Expression and subcellular location EditCSK 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 EditY184F Abolishes phosphorylation 14 Y304F Decreases activity by two thirds and alters conformation 14 S364A Strong decrease of phosphorylation by PRKACA the catalytic subunit of protein kinase A 15 Clinical significance EditCsk s interaction with a phosphatase Lyp gene product of PTPN22 is possibly associated with the increased autoimmune diseases associated with PTPN22 mutations 16 References Edit a b c GRCh38 Ensembl release 89 ENSG00000103653 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000032312 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene C src tyrosine kinase Retrieved 2013 07 11 a b Bergman 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 a b Sun 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 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 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 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 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 a b Universal protein resource accession number P41240 for Tyrosine protein kinase CSK at UniProt Brauninger A Holtrich U Strebhardt K Rubsamen 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 a b Joukov 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 Vang T Torgersen KM Sundvold V Saxena M Levy FO Skalhegg BS Hansson V Mustelin T Tasken 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 Fiorillo E Orru 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 EditCSK tyrosine protein kinase at the US National Library of Medicine Medical Subject Headings MeSH Portal Biology Retrieved from https en wikipedia org w index php title Tyrosine protein kinase CSK amp oldid 1048436586, wikipedia, wiki, book, books, library,
