Serine/threonine protein kinases phosphorylate the OH group of serine or threonine (which have similar sidechains).
Activity of these protein kinases can be regulated by specific events (e.g. DNA damage), as well as numerous chemical signals, including:
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 the substrate to be phosphorylated make contact with the catalytic cleft of the kinase at several key amino acids (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" having 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.
Many serine/threonine protein kinases do not have their own individual EC numbers
and use "188.8.131.52". These were formerly included in EC number "184.108.40.206", which was a general EC number for any enzyme that phosphorylates proteins while converting ATP to ADP (i.e. ATP:protein phosphotransferases.) This category is currently being reviewed by the Nomenclature Committee of IUBMB (NC-IUBMB), and it is believed that the various serine/threonine-kinases will get their own EC numbers eventually.
- CK2, also known by the misnomer Casein Kinase 2, was discovered in 1954 by Burnett and Kennedy.
- Phosphorylase kinase was in fact, the first Ser/Thr protein kinase to be discovered (in 1959 by Krebs et al.).
- 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.
- Protein Kinase B is 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.
- 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.
- Ca2+/calmodulin-dependent protein kinases or CaM kinases are primarily regulated by the Ca2+/calmodulin complex.
- Mitogen-activated protein kinases (MAPKs) (EC 220.127.116.11) respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis.
- 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.
- Pelle is a serine/threonine kinase that can phosphorylate itself, and also Tube and Toll.