PMID- 36764601
OWN - NLM
STAT- MEDLINE
DCOM- 20230322
LR  - 20230412
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 515
DP  - 2023 Apr 1
TI  - MNK1 and MNK2 Expression in the Human Dorsal Root and Trigeminal Ganglion.
PG  - 96-107
LID - S0306-4522(23)00064-7 [pii]
LID - 10.1016/j.neuroscience.2023.01.039 [doi]
AB  - Mitogen activated protein kinase interacting kinases (MNK) 1 and 2 are 
      serine/threonine protein kinases that play an important role in translation of 
      mRNAs through their phosphorylation of the RNA 5'-cap binding protein, eukaryotic 
      translation initiation factor (eIF) 4E. These kinases are downstream targets for 
      mitogen activated protein kinases (MAPKs), extracellular activity regulated 
      protein kinase (ERK) and p38. MNKs have been implicated in the sensitization of 
      peripheral nociceptors of the dorsal root and trigeminal ganglion (DRG and TG) 
      using transgenic mouse lines and through the use of specific inhibitors of MNK1 
      and MNK2. While specific knockout of the Mknk1 gene suggests that it is the key 
      isoform for regulation of nociceptor excitability and nociceptive behaviors in 
      mice, both MKNK1 and MKNK2 genes are expressed in the DRG and TG of mice and 
      humans based on RNA sequencing experiments. Single cell sequencing in mice 
      suggests that Mknk1 and Mknk2 may be expressed in different populations of 
      nociceptors. We sought to characterize mRNA expression in human DRG and TG (N = 3 
      ganglia for both DRG and TG) for both MNK1 and MNK2. Our results show that both 
      genes are expressed by nearly all neurons in both human ganglia with expression 
      in other cell types as well. Our findings provide evidence that MNK1 and MNK2 are 
      expressed by human nociceptors of males and females and suggest that efforts to 
      pharmacologically target MNKs for pain would likely be translatable due its 
      conserved expression in both species.
CI  - Copyright (c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Shiers, Stephanie
AU  - Shiers S
AD  - Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, 
      University of Texas at Dallas, Richardson, TX, USA.
FAU - Sahn, James J
AU  - Sahn JJ
AD  - 4E Therapeutics, Austin, TX, USA.
FAU - Price, Theodore J
AU  - Price TJ
AD  - Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, 
      University of Texas at Dallas, Richardson, TX, USA. Electronic address: 
      theodore.price@utdallas.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230209
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.1.- (MKNK1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (MKNK2 protein, human)
SB  - IM
UOF - bioRxiv. 2023 Jan 04;:. PMID: 36711529
CIN - Neuroscience. 2023 Apr 1;515:93-95. PMID: 36922084
MH  - Animals
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - *Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Spinal Nerve Roots/metabolism
MH  - *Trigeminal Ganglion/metabolism
OTO - NOTNLM
OT  - MKNK gene
OT  - MNK1
OT  - MNK2
OT  - dorsal root ganglion
OT  - nociceptor
OT  - trigeminal ganglion
EDAT- 2023/02/11 06:00
MHDA- 2023/03/21 06:00
CRDT- 2023/02/10 19:28
PHST- 2023/01/05 00:00 [received]
PHST- 2023/01/28 00:00 [revised]
PHST- 2023/01/31 00:00 [accepted]
PHST- 2023/02/11 06:00 [pubmed]
PHST- 2023/03/21 06:00 [medline]
PHST- 2023/02/10 19:28 [entrez]
AID - S0306-4522(23)00064-7 [pii]
AID - 10.1016/j.neuroscience.2023.01.039 [doi]
PST - ppublish
SO  - Neuroscience. 2023 Apr 1;515:96-107. doi: 10.1016/j.neuroscience.2023.01.039. 
      Epub 2023 Feb 9.