A serine/threonine-specific protein kinase is a kind of mitogenactivated protein kinase (MAPK or MAP kinase) that is selective for the amino acids serine and threonine. MAPKs control how cells respond to different stimuli such as osmotic stress, proinflammatory cytokines, heat shock, and mitogens. Proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis are all regulated by them. MAP kinases are only present in eukaryotes, however, they are found in a wide range of mammals, fungi, and plants, as well as a variety of unicellular eukaryotes.
Types of MAPKs
The activation of most MAPKs is dependent on two phosphorylation events, they have three-tiered pathway, and they have comparable substrate recognition sites. The "classical" MAP kinases are those that are found in the body. However, there are certain ancient outliers from the above-mentioned category that lack dual phosphorylation sites, only form two-tiered pathways, and lack the properties essential for substrate binding by other MAPKs. "Atypical" MAPKs are the name given to these types of MAPKs. It's still uncertain if atypical MAPKs and conventional MAPKs belong to the same family .
The MAPK family of kinases in mammals is divided into three subfamilies:
• Extracellular signal-regulated kinases (ERKs)
• c-Jun N-terminal Kinases (JNKs)
• p38 mitogen-activated protein kinases (p38s)
Process of MAPK activation
In their original state, mitogen-activated protein kinases are catalytically inactive. They require, possibly numerous phosphorylation events in their activation loops to become active. Specialized enzymes from the STE protein kinase group are responsible for this. Long-range allostery can be used to cause a conformational change in the structure of a protein in this way. The activation loop of conventional MAP kinases has a TxY (threonine-x-tyrosine) motif which means TEY in mammalian ERK1 and ERK2, TDY in ERK5, TPY in JNKs, TGY in p38 kinases that must be phosphorylated on both the threonine and tyrosine residues to lock the kinase domain in a cascade Phosphorylation of tyrosine generally precedes phosphorylation of threonine in vivo and in vitro, while either residue can be phosphorylated in the absence of the other. Members of the Ste7 protein kinase family, also known as MAP2 kinases, phosphorylate the tandem activation loop (which has been postulated to be either distributive or processive depending on the cellular context). Phosphorylation of MAP2 kinases by a variety of upstream serine-threonine kinases also activates MAP3 kinases. Classic MAPK pathways are multi-tiered, yet rather linear because MAP2 kinases show very limited action on substrates other than its homologous MAPK. These pathways can transport stimuli from the cell membrane, where numerous MAP3Ks are activated to the nucleus or where only MAPKs can enter or to a variety of other subcellular locations .
A number of phosphatases are involved in the inactivation of MAPKs. The MAP kinase phosphatases (MKPs), a subclass of dual-specificity phosphatases (DUSPs), are a relatively conserved family of specialized phosphatases. These enzymes can hydrolyze the phosphate from both phosphotyrosine and a phosphothreonine residue, as their name indicates. Some tyrosine phosphatases are also implicated in inactivating MAP kinases since removing either phosphate group dramatically reduces MAPK activity, thus eliminating signaling for example the phosphatases HePTP, STEP, and PTPRR in mammals [3,4].
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Citation: Cobb MH (2021) Mitogen Activated Protein Kinase: A Brief Note. J Cell Signal. 6: 262.
Received: 06-Dec-2021 Accepted: 20-Dec-2021 Published: 27-Dec-2021
Copyright: © 2021 Cobb MH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.