PMID- 36711529
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231109
DP  - 2023 Jan 4
TI  - MNK1 and MNK2 expression in the human dorsal root and trigeminal ganglion.
LID - 2023.01.04.522773 [pii]
LID - 10.1101/2023.01.04.522773 [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 5aeuro-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 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 and suggest that efforts to pharmacologically target MNKs for pain 
      would likely be translatable due its conserved expression in both species.
FAU - Shiers, Stephanie
AU  - Shiers S
AD  - Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, 
      University of Texas at Dallas, Richardson, Texas, USA.
FAU - Sahn, James J
AU  - Sahn JJ
AD  - 4E Therapeutics, Austin, Texas, 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, Texas, USA.
LA  - eng
GR  - R01 NS065926/NS/NINDS NIH HHS/United States
GR  - U44 NS115692/NS/NINDS NIH HHS/United States
PT  - Preprint
DEP - 20230104
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - Neuroscience. 2023 Feb 8;:. PMID: 36764601
PMC - PMC9881964
COIS- Conflict of Interest Statement JJS is an employee of 4E Therapeutics and TJP is a 
      founder of 4E Therapeutics, a company developing MNK inhibitors for pain 
      treatment. SS, JJS and TJP are inventors on patents related to MNK inhibition for 
      pain treatment
EDAT- 2023/01/31 06:00
MHDA- 2023/01/31 06:01
PMCR- 2023/01/27
CRDT- 2023/01/30 03:55
PHST- 2023/01/30 03:55 [entrez]
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/01/31 06:01 [medline]
PHST- 2023/01/27 00:00 [pmc-release]
AID - 2023.01.04.522773 [pii]
AID - 10.1101/2023.01.04.522773 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Jan 4:2023.01.04.522773. doi: 10.1101/2023.01.04.522773.