Serine/threonine-specific protein kinase
Protein-serine/threonine kinases | |||||||||
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ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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A serine/threonine protein kinase (
In
The chemical reaction performed by these enzymes can be written as
- ATP + a protein ADP + a phosphoprotein
Thus, the two
The systematic name of this enzyme class is ATP:protein phosphotransferase (non-specific).
Function
Serine/threonine kinases play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development.
Selectivity
While serine/threonine kinases all
EC numbers
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
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 |
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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 | 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.).
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Clinical significance
This 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
Raf inhibition has become the target for new anti-metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation.
See also
- Protein 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
- PMID 12467573.
- PMID 31875044.
- PMID 2835010.
- PMID 5456997.
- PMID 4312674.
- PMID 4310608.
- PMID 8485317.
- PMID 9102632.
- 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.
- PMID 16912193.
- PMID 27101098.
- PMID 15833840.
External links
- protein-serine-threonine+kinases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- KinCore (Kinase Conformational Resource)