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.[citation needed]
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. 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.[citation needed]
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]
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.
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.
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.
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.
respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, and cell survival/apoptosis.
was in fact, the first Ser/Thr protein kinase to be discovered (in 1959 by Krebset al.).
Clinical significance
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.[citation needed]
^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. PMID2835010.
^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. PMID5456997.
^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. PMID11267674.
^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. PMID16912193.
^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. PMID15833840.
