Serine/threonine-specific protein kinase
| Non-specific serine/threonine protein kinase | |||||||||
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| Identifiers | |||||||||
| EC number | 2.7.11.1 | ||||||||
| CAS number | 9026-43-1 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / EGO | ||||||||
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A serine/threonine protein kinase (EC 2.7.11.1) is a kinase enzyme that phosphorylates the OH group of serine or threonine (which have similar sidechains). At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK).[2]
Regulation
Serine/Threonine Kinase receptors play a role in the regulation of cell proliferation, programmed cell death (apoptosis), cell differentiation, and embryonic development.
Selectivity
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. Most 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
Many serine/threonine protein kinases do not have their own individual EC numbers and use "2.7.11.1". These were formerly included in EC number "2.7.1.37", which was a general EC number for any enzyme that phosphorylates proteins while converting ATP to ADP (i.e., ATP:protein phosphotransferases.)
Types
Types include those acting directly as receptors (Receptor protein serine/threonine kinase) and Intracellular signaling peptides and proteins. 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 | 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 2.7.11.1 | Protein kinase C ('PKC') | is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three subfamilies: | 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.
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 2.7.1.37 | Pelle | is a serine/threonine kinase that can phosphorylate itself, and also Tube and Toll. |
Clinical significance
Serine/threonine kinase (STK) expression is altered in many types of cancer.[2]
Serine/threonine protein kinase p90-kDa ribosomal S6 kinase (RSK) is in involved in development of some prostate cancers.[3]
Raf inhibition has become the target for new anti-metastatic cancer drugs as they inhibit the MAPK cascade and reduce cell proliferation.
References
- ↑ 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 (London, England : 1993) 10 (12): 1659–1667. doi:10.1016/S0969-2126(02)00907-3. PMID 12467573.
- 1 2 http://cancerres.aacrjournals.org/cgi/content/full/66/16/8147 "Frequent Alterations in the Expression of Serine/Threonine Kinases in Human Cancers" Capra et al. Cancer Research. 2006
- ↑ http://cancerres.aacrjournals.org/cgi/content/abstract/65/8/3108 "The Serine/Threonine Protein Kinase, p90 Ribosomal S6 Kinase, Is an Important Regulator of Prostate Cancer Cell Proliferation" Cancer Research. 2005
External links
- protein-serine-threonine kinases at the US National Library of Medicine Medical Subject Headings (MeSH)
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