Histone Serine/threonine/tyrosine kinases
Protein phosphorylation is the function of members of protein kinase superfamily. They harbour a characteristic kinase domain. This kinase domain catalyses the transfer of gamma-phosphate group from a donor like ATP/GTP, specifically to the serine, threonine or tyrosine residues of the protein substrates. There are a large number of protein kinases and their classification is difficult.
Protein kinases are broadly classified into:
AGC (Cyclic nucleotide-regulated protein kinase) group: These are basic amino acid directed enzymes. There substrates have serine/threonine rediues in proximity to arginine or lysine residues. Examples of some families: PKC, RAC, beta-ARK, RhK, ribosomal S6 kinase.
CaMK (Ca+/Calmodulin regulated kinases) group: These are also basic amino acid directed enzymes like AGC. Most of these enzymes are activated by Calcium or calmodulin binding to the C terminal end of the catalytic domain. Examples of some families: CaMK1/2/4, EF2K, PhK, MLCK, Snf1/AMPK.
CMGC (cyclin-dependent kinases; CDKs) group: Enzymes in this large group mostly have affinity for substrates that have target site within a proline rich environment. A characteristic of this group is the large kinase domain due to insertions. Examples of some families: cdc2, cdk2, Erk/MAP kinase, GSK3.
Protein-Tyrosine Kinase group: The members of this group are capable of exclusively phosphorylating tyrosine residues. Glutamic acid on the amino or carboxyl end of the acceptor is majorly the preferred site. They play a significant role in signal transduction. A number of enzymes in this group are membrane bound receptors. Examples of some families: HRI, PKR/Tik, Gcn2.
Others include protein kinases with dual specificity. They are capable of phosphorylating Serine/threonine as well as Tyrosine residues. Examples of some families: MEK/Ste7, Wee1/Mik1 families.
Here we list 29 unique kinases found in humans through literature that show specificity towards histones in in vitro and in vivo conditions. Protein kinases have very important role in signal transduction and are critical components of multiple signalling pathways that exist in eukaryotic cells. Hence, protein kinases are heavily implicated in many cellular processes. DNAPK, ATM, ATR, MST1 are important kinases that mediate DNA damage response by phosphorylation of histone H2AX. IKK alpha, MSK1 and MST1 directly or indirectly regulate NF-kB signalling. Other processes include DNA repair pathways, cell cycle progression, transcriptional regulation of Hox genes and E2F target genes, nuclear hormone signalling and chromatin remodelling. Protein kinases are also implicated in many cancers like prostrate cancers, gastric cancers, types of blood cancers, breast cancers. Of particular interest is WSTF that bears no homology to any tyrosine kinase fold but still catalyses tyrosine phosphorylation.
Further reading: PMID: 7768349.Cytogenetic map of Serine/threonine/tyrosine kinases coding genes