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Serine/threonine-specific protein kinase

January 01, 1970

A serine/threonine protein kinase (EC 2.7.11.-) is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK).[2]

Protein-serine/threonine kinases
Human Aurora Kinase PDB 1mq4[1]
Identifiers
EC no.2.7.11.-
CAS no.9026-43-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
serine
threonine
phosphate
phosphoserine

In enzymology, the term serine/threonine protein kinase describes a class of enzymes in the family of transferases, that transfer phosphates to the oxygen atom of a serine or threonine side chain in proteins. This process is called phosphorylation. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes and is a very important post-translational modification.[3][4][5][6][7][8][9]

The chemical reaction performed by these enzymes can be written as

ATP + a protein ADP + a phosphoprotein

Thus, the two substrates of this enzyme are ATP and a protein, whereas its two products are ADP and phosphoprotein.

The systematic name of this enzyme class is ATP:protein phosphotransferase (non-specific).

Function edit

Serine/threonine kinases play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development.

Selectivity edit

While serine/threonine kinases all phosphorylate serine or threonine residues in their substrates, they select specific residues to phosphorylate on the basis of residues that flank the phosphoacceptor site, which together comprise the consensus sequence. Since the consensus sequence residues of a target substrate only make contact with several key amino acids within the catalytic cleft of the kinase (usually through hydrophobic forces and ionic bonds), a kinase is usually not specific to a single substrate, but instead can phosphorylate a whole "substrate family" which share common recognition sequences. While the catalytic domain of these kinases is highly conserved, the sequence variation that is observed in the kinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. Many kinases are inhibited by a pseudosubstrate that binds to the kinase like a real substrate but lacks the amino acid to be phosphorylated. When the pseudosubstrate is removed, the kinase can perform its normal function.

EC numbers edit

Many serine/threonine protein kinases do not have their own individual EC numbers and use 2.7.11.1, "non-specific serine/threonine protein kinase". This entry is for any enzyme that phosphorylates proteins while converting ATP to ADP (i.e., ATP:protein phosphotransferases.)[10] 2.7.11.37 "protein kinase" was the former generic placeholder and was split into several entries (including 2.7.11.1) in 2005.[11] 2.7.11.70 "protamine kinase" was merged into 2.7.11.1 in 2004.[12]

2.7.11.- is the generic level where all serine/threonine kinases should sit in.[13]

Types edit

Types include those acting directly as membrane-bound receptors (Receptor protein serine/threonine kinase) and intracellular kinases participating in Signal transduction. Of the latter, types include:

EC number Name Description
EC 2.7.11.1 CK2, also known by the misnomer casein kinase 2 was discovered in 1954 by Burnett and Kennedy.
EC 2.7.11.1 Mos/Raf kinases form part of the MAPKK Kinase family and are activated by growth factors. The enzyme functions to stimulate growth of cells. Raf inhibition has become the target for new anti-metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation.
EC 2.7.11.1 Protein Kinase B, also known as AKT kinase The v-akt gene was identified as the oncogene of retrovirus AKT8. The gene codes for a protein kinase. Human homologs of the AKT8 oncogenic protein were identified in 1987.By 1995 it had been found that Akt kinases function as mitogen-activated kinases downstream from cell surface receptors that activate phosphoinositide 3-kinase. Three human akt genes exist. All three Akt kinases regulate cell proliferation and Akt2 is particularly important for insulin actions in cells. A major target of Akt kinases is glycogen synthase kinase-3.
EC 2.7.11.1 Pelle is a serine/threonine kinase that can phosphorylate itself, and also Tube and Toll.
EC 2.7.11.11 Protein kinase A consists of two domains, a small domain with several β sheet structures and a larger domain containing several α helices. The binding sites for substrate and ATP are located in the catalytic cleft between the domains (or lobes). When ATP and substrate bind, the two lobes rotate so that the terminal phosphate group of the ATP and the target amino acid of the substrate move into the correct positions for the catalytic reaction to take place.
EC 2.7.11.13 Protein kinase C ('PKC') is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three subfamilies: conventional (or classical), novel, and atypical based on their second messenger requirements.
EC 2.7.11.24 Mitogen-activated protein kinases (MAPKs) respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis.
EC 2.7.11.17 Ca2+/calmodulin-dependent protein kinases or CaM kinases (CAMK) are primarily regulated by the Ca2+/calmodulin complex.
EC 2.7.11.19 Phosphorylase kinase was in fact, the first Ser/Thr protein kinase to be discovered (in 1959 by Krebs et al.).

Clinical significance edit

Serine/threonine kinase (STK) expression is altered in many types of cancer.[14] Limited benefit of serine/threonine kinase inhibitors has been demonstrated in ovarian cancer[15] but studies are ongoing to evaluate their safety and efficacy.

Serine/threonine protein kinase p90-kDa ribosomal S6 kinase (RSK) is in involved in development of some prostate cancers.[16]

Raf inhibition has become the target for new anti-metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation.

See also edit

References edit

  1. ^ Nowakowski, J.; Cronin, C. N.; McRee, D. E.; Knuth, M. W.; Nelson, C. G.; Pavletich, N. P.; Rogers, J.; Sang, B. C.; Scheibe, D. N.; Swanson, R. V.; Thompson, D. A. (2002). "Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography". Structure. 10 (12): 1659–1667. doi:10.1016/S0969-2126(02)00907-3. PMID 12467573.
  2. ^ Modi, V; Dunbrack, RL (24 December 2019). "A Structurally-Validated Multiple Sequence Alignment of 497 Human Protein Kinase Domains". Scientific Reports. 9 (1): 19790. Bibcode:2019NatSR...919790M. doi:10.1038/s41598-019-56499-4. PMC 6930252. PMID 31875044.
  3. ^ Damuni Z, Reed LJ (1988). "Purification and properties of a protamine kinase and a type II casein kinase from bovine kidney mitochondria". Arch. Biochem. Biophys. 262 (2): 574–84. doi:10.1016/0003-9861(88)90408-0. PMID 2835010.
  4. ^ Baggio B, Pinna LA, Moret V, Siliprandi N (1970). "A simple procedure for the purification of rat liver phosvitin kinase". Biochim. Biophys. Acta. 212 (3): 515–7. doi:10.1016/0005-2744(70)90261-5. PMID 5456997.
  5. ^ Jergil B, Dixon GH (1970). "Protamine kinase from rainbow trout testis. Partial purification and characterization". J. Biol. Chem. 245 (2): 425–34. doi:10.1016/S0021-9258(18)63408-8. PMID 4312674.
  6. ^ Langan TA (1969). "Action of adenosine 3',5'-monophosphate-dependent histone kinase in vivo". J. Biol. Chem. 244 (20): 5763–5. doi:10.1016/S0021-9258(18)63626-9. PMID 4310608.
  7. ^ Takeuchi M, Yanagida M (1993). "A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization". Mol. Biol. Cell. 4 (3): 247–60. doi:10.1091/mbc.4.3.247. PMC 300923. PMID 8485317.
  8. ^ NF; Lützelberger, M; Weigmann, H; Klingenhoff, A; Shenoy, S; Käufer, NF (1997). "Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue". Nucleic Acids Res. 25 (5): 1028–35. doi:10.1093/nar/25.5.1028. PMC 146536. PMID 9102632.
  9. ^ Wang Y, Hofmann TG, Runkel L, Haaf T, Schaller H, Debatin K, Hug H (2001). "Isolation and characterization of cDNAs for the protein kinase HIPK2". Biochim. Biophys. Acta. 1518 (1–2): 168–72. doi:10.1016/S0167-4781(00)00308-0. PMID 11267674.
  10. ^ "ENZYME - 2.7.11.1 non-specific serine/threonine protein kinase". enzyme.expasy.org. Retrieved 2023-12-25.
  11. ^ "KEGG ENZYME: 2.7.1.37". www.genome.jp. Retrieved 2023-12-25.
  12. ^ "KEGG ENZYME: 2.7.1.70". www.genome.jp. Retrieved 2023-12-25.
  13. ^ "EC 2.7.11". iubmb.qmul.ac.uk. Retrieved 2023-12-25.
  14. ^ Capra, Maria; Nuciforo, Paolo Giovanni; Confalonieri, Stefano; Quarto, Micaela; Bianchi, Marco; Nebuloni, Manuela; Boldorini, Renzo; Pallotti, Francesco; Viale, Giuseppe; Gishizky, Mikhail L.; Draetta, Giulio F.; Fiore, Pier Paolo Di (15 August 2006). "Frequent Alterations in the Expression of Serine/Threonine Kinases in Human Cancers". Cancer Research. 66 (16): 8147–8154. doi:10.1158/0008-5472.CAN-05-3489. PMID 16912193.
  15. ^ Ciccone, Marcia A.; Maoz, Asaf; Casabar, Jennifer K.; Machida, Hiroko; Mabuchi, Seiji; Matsuo, Koji (2 July 2016). "Clinical outcome of treatment with serine-threonine kinase inhibitors in recurrent epithelial ovarian cancer: a systematic review of literature". Expert Opinion on Investigational Drugs. 25 (7): 781–796. doi:10.1080/13543784.2016.1181748. PMC 7534810. PMID 27101098.
  16. ^ Clark, D. E.; Errington, T. M.; Smith, J. A.; Frierson, H. F.; Weber, M. J.; Lannigan, D. A. (15 April 2005). "The Serine/Threonine Protein Kinase, p90 Ribosomal S6 Kinase, Is an Important Regulator of Prostate Cancer Cell Proliferation". Cancer Research. 65 (8): 3108–3116. doi:10.1158/0008-5472.CAN-04-3151. PMID 15833840.

External links edit

  • protein-serine-threonine+kinases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • KinCore (Kinase Conformational Resource)

January 01, 1970
serine, threonine, specific, protein, kinase, serine, threonine, protein, kinase, kinase, enzyme, particular, protein, kinase, that, phosphorylates, group, amino, acid, residues, serine, threonine, which, have, similar, side, chains, least, human, protein, kin. A serine threonine protein kinase EC 2 7 11 is a kinase enzyme in particular a protein kinase that phosphorylates the OH group of the amino acid residues serine or threonine which have similar side chains At least 350 of the 500 human protein kinases are serine threonine kinases STK 2 Protein serine threonine kinasesHuman Aurora Kinase PDB 1mq4 1 IdentifiersEC no 2 7 11 CAS no 9026 43 1DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteins serine threonine phosphate phosphoserine In enzymology the term serine threonine protein kinase describes a class of enzymes in the family of transferases that transfer phosphates to the oxygen atom of a serine or threonine side chain in proteins This process is called phosphorylation Protein phosphorylation in particular plays a significant role in a wide range of cellular processes and is a very important post translational modification 3 4 5 6 7 8 9 The chemical reaction performed by these enzymes can be written as ATP a protein displaystyle rightleftharpoons ADP a phosphoprotein Thus the two substrates of this enzyme are ATP and a protein whereas its two products are ADP and phosphoprotein The systematic name of this enzyme class is ATP protein phosphotransferase non specific Contents 1 Function 2 Selectivity 3 EC numbers 4 Types 5 Clinical significance 6 See also 7 References 8 External linksFunction editSerine threonine kinases play a role in the regulation of cell proliferation programmed cell death apoptosis cell differentiation and embryonic development Selectivity editWhile serine threonine kinases all phosphorylate serine or threonine residues in their substrates they select specific residues to phosphorylate on the basis of residues that flank the phosphoacceptor site which together comprise the consensus sequence Since the consensus sequence residues of a target substrate only make contact with several key amino acids within the catalytic cleft of the kinase usually through hydrophobic forces and ionic bonds a kinase is usually not specific to a single substrate but instead can phosphorylate a whole substrate family which share common recognition sequences While the catalytic domain of these kinases is highly conserved the sequence variation that is observed in the kinome the subset of genes in the genome that encode kinases provides for recognition of distinct substrates Many kinases are inhibited by a pseudosubstrate that binds to the kinase like a real substrate but lacks the amino acid to be phosphorylated When the pseudosubstrate is removed the kinase can perform its normal function EC numbers editMany serine threonine protein kinases do not have their own individual EC numbers and use 2 7 11 1 non specific serine threonine protein kinase This entry is for any enzyme that phosphorylates proteins while converting ATP to ADP i e ATP protein phosphotransferases 10 2 7 11 37 protein kinase was the former generic placeholder and was split into several entries including 2 7 11 1 in 2005 11 2 7 11 70 protamine kinase was merged into 2 7 11 1 in 2004 12 2 7 11 is the generic level where all serine threonine kinases should sit in 13 Types editTypes include those acting directly as membrane bound receptors Receptor protein serine threonine kinase and intracellular kinases participating in Signal transduction Of the latter types include EC number Name Description EC 2 7 11 1 CK2 also known by the misnomer casein kinase 2 was discovered in 1954 by Burnett and Kennedy EC 2 7 11 1 Mos Raf kinases form part of the MAPKK Kinase family and are activated by growth factors The enzyme functions to stimulate growth of cells Raf inhibition has become the target for new anti metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation EC 2 7 11 1 Protein Kinase B also known as AKT kinase The v akt gene was identified as the oncogene of retrovirus AKT8 The gene codes for a protein kinase Human homologs of the AKT8 oncogenic protein were identified in 1987 By 1995 it had been found that Akt kinases function as mitogen activated kinases downstream from cell surface receptors that activate phosphoinositide 3 kinase Three human akt genes exist All three Akt kinases regulate cell proliferation and Akt2 is particularly important for insulin actions in cells A major target of Akt kinases is glycogen synthase kinase 3 EC 2 7 11 1 Pelle is a serine threonine kinase that can phosphorylate itself and also Tube and Toll EC 2 7 11 11 Protein kinase A consists of two domains a small domain with several b sheet structures and a larger domain containing several a helices The binding sites for substrate and ATP are located in the catalytic cleft between the domains or lobes When ATP and substrate bind the two lobes rotate so that the terminal phosphate group of the ATP and the target amino acid of the substrate move into the correct positions for the catalytic reaction to take place EC 2 7 11 13 Protein kinase C PKC is actually a family of protein kinases consisting of 10 isozymes They are divided into three subfamilies conventional or classical novel and atypical based on their second messenger requirements EC 2 7 11 24 Mitogen activated protein kinases MAPKs respond to extracellular stimuli mitogens and regulate various cellular activities such as gene expression mitosis differentiation and cell survival apoptosis EC 2 7 11 17 Ca2 calmodulin dependent protein kinases or CaM kinases CAMK are primarily regulated by the Ca2 calmodulin complex EC 2 7 11 19 Phosphorylase kinase was in fact the first Ser Thr protein kinase to be discovered in 1959 by Krebs et al Clinical significance editThis section needs expansion You can help by adding to it December 2008 Serine threonine kinase STK expression is altered in many types of cancer 14 Limited benefit of serine threonine kinase inhibitors has been demonstrated in ovarian cancer 15 but studies are ongoing to evaluate their safety and efficacy Serine threonine protein kinase p90 kDa ribosomal S6 kinase RSK is in involved in development of some prostate cancers 16 Raf inhibition has become the target for new anti metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation See also editProtein serine threonine phosphatase enzyme for reverse process Pseudokinase a protein without enzyme activity pseudoenzyme It can be related to proteins of this class ATM serine threonine kinase responsible for the disorder ataxia telangiectasia References edit Nowakowski J Cronin C N McRee D E Knuth M W Nelson C G Pavletich N P Rogers J Sang B C Scheibe D N Swanson R V Thompson D A 2002 Structures of the cancer related Aurora A FAK and EphA2 protein kinases from nanovolume crystallography Structure 10 12 1659 1667 doi 10 1016 S0969 2126 02 00907 3 PMID 12467573 Modi V Dunbrack RL 24 December 2019 A Structurally Validated Multiple Sequence Alignment of 497 Human Protein Kinase Domains Scientific Reports 9 1 19790 Bibcode 2019NatSR 919790M doi 10 1038 s41598 019 56499 4 PMC 6930252 PMID 31875044 Damuni Z Reed LJ 1988 Purification and properties of a protamine kinase and a type II casein kinase from bovine kidney mitochondria Arch Biochem Biophys 262 2 574 84 doi 10 1016 0003 9861 88 90408 0 PMID 2835010 Baggio B Pinna LA Moret V Siliprandi N 1970 A simple procedure for the purification of rat liver phosvitin kinase Biochim Biophys Acta 212 3 515 7 doi 10 1016 0005 2744 70 90261 5 PMID 5456997 Jergil B Dixon GH 1970 Protamine kinase from rainbow trout testis Partial purification and characterization J Biol Chem 245 2 425 34 doi 10 1016 S0021 9258 18 63408 8 PMID 4312674 Langan TA 1969 Action of adenosine 3 5 monophosphate dependent histone kinase in vivo J Biol Chem 244 20 5763 5 doi 10 1016 S0021 9258 18 63626 9 PMID 4310608 Takeuchi M Yanagida M 1993 A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization Mol Biol Cell 4 3 247 60 doi 10 1091 mbc 4 3 247 PMC 300923 PMID 8485317 NF Lutzelberger M Weigmann H Klingenhoff A Shenoy S Kaufer NF 1997 Functional analysis of the fission yeast Prp4 protein kinase involved in pre mRNA splicing and isolation of a putative mammalian homologue Nucleic Acids Res 25 5 1028 35 doi 10 1093 nar 25 5 1028 PMC 146536 PMID 9102632 Wang Y Hofmann TG Runkel L Haaf T Schaller H Debatin K Hug H 2001 Isolation and characterization of cDNAs for the protein kinase HIPK2 Biochim Biophys Acta 1518 1 2 168 72 doi 10 1016 S0167 4781 00 00308 0 PMID 11267674 ENZYME 2 7 11 1 non specific serine threonine protein kinase enzyme expasy org Retrieved 2023 12 25 KEGG ENZYME 2 7 1 37 www genome jp Retrieved 2023 12 25 KEGG ENZYME 2 7 1 70 www genome jp Retrieved 2023 12 25 EC 2 7 11 iubmb qmul ac uk Retrieved 2023 12 25 Capra Maria Nuciforo Paolo Giovanni Confalonieri Stefano Quarto Micaela Bianchi Marco Nebuloni Manuela Boldorini Renzo Pallotti Francesco Viale Giuseppe Gishizky Mikhail L Draetta Giulio F Fiore Pier Paolo Di 15 August 2006 Frequent Alterations in the Expression of Serine Threonine Kinases in Human Cancers Cancer Research 66 16 8147 8154 doi 10 1158 0008 5472 CAN 05 3489 PMID 16912193 Ciccone Marcia A Maoz Asaf Casabar Jennifer K Machida Hiroko Mabuchi Seiji Matsuo Koji 2 July 2016 Clinical outcome of treatment with serine threonine kinase inhibitors in recurrent epithelial ovarian cancer a systematic review of literature Expert Opinion on Investigational Drugs 25 7 781 796 doi 10 1080 13543784 2016 1181748 PMC 7534810 PMID 27101098 Clark D E Errington T M Smith J A Frierson H F Weber M J Lannigan D A 15 April 2005 The Serine Threonine Protein Kinase p90 Ribosomal S6 Kinase Is an Important Regulator of Prostate Cancer Cell Proliferation Cancer Research 65 8 3108 3116 doi 10 1158 0008 5472 CAN 04 3151 PMID 15833840 External links editprotein serine threonine kinases at the U S National Library of Medicine Medical Subject Headings MeSH KinCore Kinase Conformational Resource Portal nbsp Biology Retrieved from https en wikipedia org w index php title Serine threonine specific protein kinase amp oldid 1196442089, wikipedia, wiki, book, books, library,

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