Taste receptor type 2 member 14 is aprotein that in humans is encoded by theTAS2R14gene.[5][6][7]
Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family ofG-protein coupled receptors and are related toclass A-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.[8]
Bitter taste receptor hTAS2R14 is one of the human bitter taste receptors, recognizing an enormous variety of structurally different molecules, including natural and synthetic bitter compounds.[9]
TAS2R14gene[5][7] (Taste receptor type 2 member 14) is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12p13.[10]
TAS2Rs activation produces modulation of a broad range of signal transduction pathways. The Gαgusducin (Gαgus), which belongs to theGαi subfamily, was first identified and cloned in 1992 intaste tissue, and has high similarity to the Gα-transducin (Gαtrans) in the retina.Gα16gus44, a chimeric Gα16 (type of Gαq), harboring 44 gustducin specific sequence at its C terminus, or Gαqi5, a Gαq protein containing the five carboxyl-terminal amino acids from Gαi, are often used in order to couple the taste receptor to Gαq pathway and measure calcium or IP3 release.Specifically, stimulation of aGPCR receptor, coupled to Gαq, results in the activation of phospholipase C β2 (PLC), which then stimulates the second messengers 1,4,5-inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 causes the release of Ca+2 from intracellular stores. Calcium opens Ca-activated TRP ion channels and leads to depolarization of the cell as well as to release of neurotransmitters.[13]
To date, 151 ligands have been identified for T2R14,[14][15] in addition to 12 syntheticflufenamic acid derivatives.[16]TAS2R14 agonist 28.1 is one of the most potent agonists yet developed for this target.[17]
This gene product belongs to the family oftaste receptors that are members of theG-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, TAS2R14 responds to (−)-α-thujone, the primary neurotoxic agent inabsinthe, andpicrotoxin, a poison found in fishberries.[27] This gene maps to the taste receptor gene cluster on chromosome 12p13.[7]
TAS2R14 is also expressed in thesmooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellularcalcium ion, which in turn triggers the opening ofpotassium channels whichhyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads tobronchodilation.[28]
In the respiratory system, several TAS2R subtypes: TAS2R4, TAS2R16, TAS2R14 and TAS2R38, were found to play important roles in innate immune nitric oxide production (NO).[29]
T2R14 causes inhibition of IgE-dependent mast cells.[30]
^Di Pizio A, Niv MY (July 2015). "Promiscuity and selectivity of bitter molecules and their receptors".Bioorganic & Medicinal Chemistry.23 (14):4082–4091.doi:10.1016/j.bmc.2015.04.025.PMID25934224.
^Nowak S, Di Pizio A, Levit A, Niv MY, Meyerhof W, Behrens M (October 2018). "Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14".Biochimica et Biophysica Acta (BBA) - General Subjects.1862 (10):2162–2173.doi:10.1016/j.bbagen.2018.07.009.PMID30009876.S2CID51628536.
^Ballesteros JA, Weinstein H (January 1995).[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods in Neurosciences. Vol. 25. pp. 366–428.doi:10.1016/S1043-9471(05)80049-7.ISBN978-0-12-185295-5.ISSN1043-9471.
^Martin LT, Nachtigal MW, Selman T, Nguyen E, Salsman J, Dellaire G, et al. (April 2019). "Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival".Molecular and Cellular Biochemistry.454 (1–2):203–214.doi:10.1007/s11010-018-3464-z.PMID30350307.S2CID53035462.
^Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W (June 2004). "The human taste receptor hTAS2R14 responds to a variety of different bitter compounds".Biochemical and Biophysical Research Communications.319 (2):479–485.doi:10.1016/j.bbrc.2004.05.019.PMID15178431.
