| Protein-serine/threonine kinases | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||||
| EC no. | 2.7.11.- | ||||||||
| CAS no. | 9026-43-1 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDBPDBePDBsum | ||||||||
| Gene Ontology | AmiGO /QuickGO | ||||||||
| |||||||||
Aserine/threonine protein kinase (EC2.7.11.-) is akinaseenzyme, in particular aprotein kinase, thatphosphorylates theOH group of theamino-acid residuesserine orthreonine, which have similar side chains. At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK).[2]
Inenzymology, the termserine/threonine protein kinase describes a class ofenzymes in the family oftransferases, that transfer phosphates to theoxygen atom of aserine orthreonine side chain inproteins. This process is calledphosphorylation. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes and is a very importantpost-translational modification.[3][4][5][6][7][8][9]
The chemical reaction performed by these enzymes can be written as
Thus, the twosubstrates of this enzyme areATP and aprotein, whereas its twoproducts areADP andphosphoprotein.
Thesystematic name of this enzyme class isATP:protein phosphotransferase (non-specific).
Serine/threonine kinases play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development.[citation needed]
While serine/threonine kinases allphosphorylate 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 theconsensus 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 throughhydrophobic forces andionic 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 thecatalytic domain of these kinases ishighly conserved, the sequence variation that is observed in thekinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. Many kinases are inhibited by apseudosubstrate 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.[citation needed]
Many serine/threonine protein kinases do not have their own individualEC 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 include those acting directly as membrane-bound receptors (Receptor protein serine/threonine kinase) and intracellular kinases participating inSignal transduction. Of the latter, types include:
| EC number | Name | Description |
|---|---|---|
| EC2.7.11.1 | CK2, also known by the misnomercasein kinase 2 | was discovered in 1954 by Burnett and Kennedy. |
| EC2.7.11.1 | 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. |
| EC2.7.11.1 | Protein Kinase B, also known asAKT kinase | The v-akt gene was identified as theoncogene ofretrovirus 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 activatephosphoinositide 3-kinase. Three human akt genes exist. All three Akt kinases regulate cell proliferation and Akt2 is particularly important forinsulin actions in cells. A major target of Akt kinases isglycogen synthase kinase-3. |
| EC2.7.11.1 | Pelle | is a serine/threonine kinase that can phosphorylate itself, and also Tube and Toll. |
| EC2.7.11.11 | Protein kinase A | consists of two domains, a small domain with severalβ sheet structures and a larger domain containing severalα 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. |
| EC2.7.11.13 | Protein kinase C ('PKC') | is actually a family of protein kinases consisting of ~10isozymes. They are divided into three subfamilies: conventional (or classical), novel, and atypical based on their second messenger requirements. |
| EC2.7.11.24 | 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. |
| EC2.7.11.17 | Ca2+/calmodulin-dependent protein kinases or CaM kinases (CAMK) | are primarily regulated by the Ca2+/calmodulin complex. |
| EC2.7.11.19 | Phosphorylase kinase | was in fact, the first Ser/Thr protein kinase to be discovered (in 1959 byKrebset al.). |
Serine/threonine kinase (STK) expression is altered in many types ofcancer.[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.[citation needed]
Serine/threonine protein kinase p90-kDaribosomal S6 kinase (RSK) is in involved in development of someprostate cancers.[16]
Raf inhibition has become the target for newanti-metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation.[citation needed]
